evaluating the real-world representativeness of
TRANSCRIPT
297CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
ABSTRACT
Background
Studies of mild cognitive impairment (MCI) employ rigor-ous eligibility criteria, resulting in sampling that may not be representative of the broader clinical population.
Objective
To compare the characteristics of MCI patients in a Calgary memory clinic to those of MCI participants in published Canadian studies.
Methods
Clinic participants included 555 MCI patients from the PROspective Registry of Persons with Memory SyMPToms (PROMPT) registry in Calgary. Research participants in-cluded 4,981 individuals with MCI pooled from a systematic literature review of 112 original, English-language peer-reviewed Canadian studies. Both samples were compared on baseline sociodemographic variables, medical and psychiatric comorbidities, and cognitive performance for MCI due to Alzheimer’s disease and Parkinson’s disease.
Results
Overall, clinic patients tended to be younger, more often male, and more educated than research participants. Psychiatric dis-orders, traumatic brain injury, and sensory impairment were commonplace in PROMPT (up to 83% affected) but > 80% studies in the systematic review excluded these conditions. PROMPT patients also performed worse on global cognition measures than did research participants.
Conclusion
Stringent eligibility criteria in Canadian research studies ex-cluded a considerable subset of MCI patients with comorbid medical or psychiatric conditions. This exclusion may con-tribute to differences in cognitive performance and outcomes compared to real-world clinical samples.
Key words: mild cognitive impairment, exclusion criteria, generalizability
INTRODUCTION
The field of dementia research is focused increasingly on an early phase conceptualized as mild cognitive impairment (MCI).(1) MCI research has significantly advanced the diag-nosis, prognosis, and prevention for this condition; however, translating results of this research to practice remains a challenge. Despite the value of past research, MCI partici-pant pools meet rigorous inclusion and exclusion criteria designed to minimize potential confounders and diagnostic errors, resulting in biased case identification(2) and sampling that is not representative of the broader clinical population. Researchers in many fields(2-6) have begun to acknowledge this misalignment between individuals enrolled in research protocols and those with the condition of interest in real-world samples. The representativeness of MCI research and clinic samples has not been quantified in a Canadian context. Given that medical(7) and psychiatric disorders(8) are common in older Canadians and associated with dementia-related out-comes,(9-11) it is important to understand how excluding these
Evaluating the Real-World Representativeness of Participants with Mild Cognitive Impairment in Canadian Research Protocols: a Comparison of the Characteristics of a Memory Clinic Patients and Research SamplesVivian Huang, PhD1, David B. Hogan, MD2,3, Zahinoor Ismail, MD2,3,4,7, Colleen J. Maxwell, PhD3,5, Eric E. Smith, MD2,3, Brandy L. Callahan, PhD3,4,6
1Department of Psychology, Ryerson University, Toronto, ON; 2Cumming School of Medicine, University of Calgary, Calgary, AB; 3Hotchkiss Brain Institute, Calgary, AB; 4Mathison Centre for Mental Health Research & Education, Calgary, AB; 5Schools of Pharmacy and Public Health & Health Systems, University of Waterloo, Waterloo, ON; 6Department of Psychology, University of Calgary, Calgary, AB; 7Department of Psychiatry, University of Calgary, Calgary, AB, Canada
https://doi.org/10.5770/cgj.23.416
ORIGINAL RESEARCH
© 2020 Author(s). Published by the Canadian Geriatrics Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No-Derivative license (http://creativecommons.org/licenses/by-nc-nd/2.5/ca/), which permits unrestricted non-commercial use and distribution, provided the original work is properly cited.
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298CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
cases from MCI research samples could impact findings and the ability to generalize them to clinical practice in a Canad-ian context. Such exclusion seems particularly relevant as a growing proportion of cases seen in Canadian memory clinics (for example, in Calgary(12)) have MCI, relative to dementia, which was more common in earlier decades.(13)
This study compared the characteristics of MCI patients in a Calgary memory clinic to those of MCI participants in published Canadian studies. We focused primarily on a clini-cal, rather than population-based, sample because we were interested in how the representativeness of research cohorts may impact generalizability to clinical practice. We acknow-ledge that clinical samples may not resemble the broader population in terms of disease severity and prognosis.(14) Given findings from other literature,(2-6) it was hypothesized that memory clinic patients would be more racially diverse, have fewer years of education, more medical and psychiatric comorbidities, and lower scores on baseline cognitive meas-ures, relative to those enrolled in research studies.
METHODS
Data were drawn from two sources: clinic participants from the PROspective Registry of Persons with Memory SyMP-Toms (PROMPT) registry(15) in Calgary, and research par-ticipants derived from a literature review of Canadian MCI cohorts. The PROMPT registry was selected as convenience sample due to data availability and accessibility. Variables of interest included sociodemographic data (age, sex, educa-tion, race), medical issues (cardiovascular/cerebrovascular disease, traumatic brain injury [TBI], vascular risk factors, neurological disorders, sensory impairment, neurological signs), psychiatric comorbidities (mood, anxiety, psychotic and substance abuse disorders, as well as current depressive symptoms) and cognitive performance (Mini-Mental State Examination [MMSE](16) and Montreal Cognitive Assess-ment [MoCA](17)).
Patient Population
The PROMPT registry(15) comprises patients from the Uni-versity of Calgary Cognitive Neurosciences Clinic that offers consultation, assessment, and follow-up services to referred patients with suspected cognitive impairment. All referred patients are eligible for inclusion in the registry with > 90% consenting to enrolment, making it highly representative of the clientele served. In this study, we only included patients initially diagnosed with MCI per the National Institute on Aging and the Alzheimer’s Association (NIA-AA) core criteria(18) including: 1) cognitive concern; 2) impairment in ≥ 1 cognitive domain; 3) preserved function; and 4) no dementia. Suspected etiologies were determined based on published reports and criteria,(19-21) pre-existing diagnosis,(22) neuroimaging evidence,(23) and the presence of any core or suggestive features of the etiologies based on psychiatric and physical assessments. MCI was considered due to Alzheimer’s disease (MCI-AD) if memory was primarily affected with
longitudinal evidence of decline and no major vascular, trau-matic or other medical causes.(18) The etiology was considered due to Parkinson’s disease (MCI-PD) when there was a pre-existing diagnosis of PD, and to vascular cognitive impairment (MCI-VCI) when there was neuroimaging(23) evidence of vascular insult or history of stroke that was felt sufficient to account for the cognitive issues (this was consistent with cri-teria from the American Heart Association/American Stroke Association criteria).(23) Other suspected etiologies of MCI included frontotemporal lobar degeneration,(19) Lewy body disease,(20) corticobasal degeneration,(21) and progressive supranuclear palsy.(22) Sociodemographic information and physician-diagnosed disorders were obtained from patient, informant, and medical records. The 15-item Geriatric Depression Scale (GDS-15)(24) assessed current depressive symptoms. The MMSE(16) and MoCA(17) assessed general cognition.
Research Participant Population
The systematic review was conducted in accordance with PRISMA guidelines.(25,26) Medline, PsychINFO, EMBASE, and PubMed were searched for studies published prior to July 2018 using the terms: (MCI OR “mild cognitive im-pairment”) AND (Canada[Affiliation/Location]). Inclusion criteria were: 1) English-language; 2) original peer-reviewed research; 3) participants exclusively recruited within Canada; 4) MCI diagnosed using formal criteria (e.g., Petersen’s(27) or NIA-AA(18)); and 5) results contained extractable MMSE and/or MoCA scores. When several studies reported on the same dataset, only the largest sample was retained to ensure sample independence. Case studies and multinational studies merging Canadian and non-Canadian data were excluded. Baseline data were used for studies with multiple time points. Four independent reviewers assessed titles, abstracts, and full texts (on selected articles) for eligibility. Two independent reviewers extracted study and sample characteristics. A third independent reviewer resolved any discrepancies.
Statistics
Descriptive statistics were computed on baseline character-istics of PROMPT patients. Cases with missing data were excluded pairwise from analyses, and no attempt was made to impute data. Cohen’s kappa (κ) assessed interreviewer agreement in the systematic review. Descriptive statistics were generated from the weighted mean and standard deviation of age, education, MMSE, and MoCA scores ( Appendix A). To compare clinic and research samples, chi-square tests with Yates correction and independent samples t-tests using weighted means were conducted. Given the most studied suspected etiologies of MCI in the literature were AD or PD (see Results), only these cases were retained from PROMPT and used in comparative analyses. All tests were two-tailed, α = 0.05, and 95% confidence intervals were used to determine statistical significance of differences found between samples. The University of Calgary’s Conjoint Health Research Ethics Board approved the study (REB18-1007).
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299CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
RESULTS
MCI Clinic Patients
A total of 555 PROMPT patients were diagnosed with MCI (mean age = 65.2, SD = 10.2; mean education = 13.49, SD = 3.41; 56.2% male). As demonstrated in Table 1, there was substantial heterogeneity in the suspected etiologies for MCI found among PROMPT patients. Physical and psychiatric comorbidities, sensory impairment, and traumatic brain injury were common, and 83% of the overall sample had at least 1 of these conditions.
MCI Research Participants
The literature search resulted in 1,122 potentially relevant arti-cles. After removing duplicates, applying inclusion criteria, and ensuring independence of samples, a total of 112 studies were retained with a total of 4,981 participants (Figure 1). Cohen’s κ coefficients were 0.76 (95% CI [0.71, 0.80]) for the title and abstract review stage, and 0.71 (95% CI [0.62, 0.80]) for the full-text review stage, indicating moderate reviewer agreement. All study characteristics are reported in Appendix B . The retained research studies included 102 observational studies, 6 randomized controlled trials (RCT), 2 non-randomized feasibility studies, 1 randomized feasibility study, and 1 retro-spective chart review. Fourteen studies(28-41) (12.5%) did not mention any inclusion/exclusion criteria and five(42-46) (4.5%) had criteria that were not specific to medical or psychiatric conditions. The remaining 93 (83.9%) explicitly excluded select medical, psychiatric, or neurological conditions. De-pression and alcohol/substance use concerns were the most frequent exclusionary conditions in 17.0% and 38.4% of pub-lished studies, respectively; an additional 25.0% of studies did not specify the psychiatric conditions that were exclusionary. All but one study(44) focused on MCI-AD (N = 4,881) or MCI-PD (N = 100), thus comparisons with PROMPT patients only refer to these MCI subtypes. One study(44) (N = 20) included MCI-VCI, but no comparison analyses were conducted due to the small sample size.
Clinic vs. Research Participants with MCI-AD and MCI-PD
MCI-AD was diagnosed in 148 PROMPT cases (26.7%), while MCI-PD was diagnosed in 12 (2.2%). Missing data in these cases ranged from 0.7–35.8% for MCI-AD cases (data were primarily missing for current [35.8%] or past [33.8%] history of alcohol abuse, and GDS-15 score [24.8%]), and 18.2–54.5% for MCI-PD cases (mostly missing for current [54.5%] or past [54.5%] history of alcohol abuse, education [27.3%], and GDS-15, MMSE, and MoCA scores [each 18.2%]). Data were missing at random (Little’s missing com-pletely at random test: χ2
(151) = 169.98, p =.14; χ2(31) = 24.02,
p = .81 for MCI-AD and MCI-PD, respectively).MCI-AD clinic patients were younger, more often male,
and more educated than research participants (Table 2). Dyslipidemia and other medical conditions (e.g., cancer, osteoporosis) were more common among clinic than re-search participants, except for hypertension which was more
prevalent among research participants. TBI, psychiatric disorders, and sensory impairment were either not reported or explicitly excluded from all research studies. At least one of these conditions was present in 66.2% of MCI-AD clinic patients. The samples also differed on MMSE and MoCA scores, with clinic patients performing worse on both tests. Further, Cohen’s effect size values (d/h ranges from 0.22 to 1.27) suggested a small to large practical significance for the aforementioned differences found between clinic patients and research participants.
MCI-PD clinic patients were more educated than research participants, but not different on age or sex (Table 3). TBI, psychiatric disorders, and sensory impairment were again absent from all research studies, and at least one of these conditions was present in 83.3% of MCI-PD clinic patients. Clinic patients also had marginally lower MoCA scores but similar MMSE scores. Further, Cohen’s effect size values (d/h ranges from 0.53 to 1.77) suggested a moderate to large prac-tical significance for the aforementioned differences found between clinic patients and research participants.
DISCUSSION
Results from this study indicate that Canadian research par-ticipants are not fully representative of MCI patients seen at a local memory clinic, with significant sociodemographic and clinical differences between samples that co-occur with differences in cognitive performance.
Contrary to a priori hypotheses and past findings,(2,4,5) clinic patients were more educated than research participants. It is possible that Quebecois participants, who comprised the majority of published samples, obtained lower total years of schooling despite comparable educational level attained due to province-specific differences(47) (e.g., high school is complete after 11 years in Quebec but 12–13 years elsewhere in Canada). These findings may also be attributed to higher average educational attainment in Calgary as a major site of migration due to job prospects in certain industries (e.g., oil and gas and health care) compared to other major Canadian cities,(48,49) or may reflect cohort differences and secular trends towards higher education in younger generations. Moreover, research studies with a cognitive assessment component may need to make a concerted effort to include individuals with diverse educational backgrounds to avoid ceiling effects as the general population becomes more educated. Regarding sex, there were more men among clinic patients than among research participants. This result is consistent with unbal-anced sex distributions in research studies, in which females are typically overrepresented.(50) The potential sex (and, perhaps, gender) differences related to MCI are not fully known. Given mixed results with respect to sex differences in the prevalence and prognosis of MCI,(51-55) future research should aim to systematically examine possible vulnerabilities in older men and women.
In both samples, most individuals were Caucasian. Ra-cial and ethnic minority status has previously been shown to
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
300CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
TAB
LE 1
. So
ciod
emog
raph
ic a
nd h
ealth
cha
ract
eris
tics o
f MC
I cas
es in
the
PRO
MPT
regi
stry
by
etio
logy
M
CI-
ADM
CI-
PDM
CI-
FTLD
MC
I-D
LBM
CI-
VCI
MC
I-C
AAM
CI-
DEP
MC
I-M
DM
CI-
PSY
MC
I-C
BGD
MC
I-PS
PM
CI-
Oth
erM
CI-
UN
SP
n =
148
(2
6.7%
of
tota
l)
n =
12
(2.2
%)
n =
44
(7.9
%)
n =
12
(2.2
%)
n =
121
(2
1.8%
)n
= 7
(1.3
%)
n =
126
(2
2.7%
)n
= 3
9 (7
.0%
)n
=56
(1
0.1%
)n
= 8
(1.4
%)
n =
6 (1
.1%
)n
= 5
6 (1
0.1%
)n
= 1
52
(27.
4%)
Age
, yea
rs68
.61
(9
.47)
66.9
4
(6.2
8)64
.03
(9
.01)
63.1
0
(5.7
5)68
.20
(8
.96)
73.8
6
(5.9
7)62
.29
(6
.77)
72.3
1
(8.1
5)61
.41
(7
.47)
64.5
2
(5.0
6)67
.60
(7
.56)
62.9
0
(7.3
0)65
.62
(8
.03)
Sex,
n (%
) Fe
mal
e60
(40.
5%)
2 (1
6.7%
)17
(39.
5%)
3 (2
5.0%
)48
(40.
3%)
3 (4
2.9%
)63
(50.
8%)
11 (2
8.9%
)30
(53.
6%)
4 (5
0.0%
)4
(66.
7%)
26 (4
6.4%
)67
(44.
4%)
Mal
e87
(59.
2%)
10 (8
3.3%
)26
(60.
5%)
9 (7
5.0%
)71
(59.
7%)
4 (5
7.1%
)61
(49.
2%)
27 (7
1.1%
)26
(46.
4%)
4 (5
0.0%
)2
(33.
3%)
30 (5
3.6%
)84
(55.
6%)
Mis
sing
1 (0
.7%
)1
(2.3
%)
2 (1
.7%
)2
(1.6
%)
1 (2
.6%
)1
(0.7
%)
Educ
atio
n, y
ears
13
.74
(3.9
7)17
.67
(4.2
3)13
.78
(3.1
2)12
.80
(2.3
6)12
.63
(2.1
9)11
.86
(2
.16)
13.4
3 (2
.60)
11.6
8 (2
.32)
12.5
5 (1
.75)
12.8
6
(2.1
2)12
.40
(7
.28)
13.7
7 (2
.38)
13.0
7
(2.3
6)
Rac
e, n
(%)
Cau
casi
an13
2 (8
9.2%
)9
(7
5.0%
)42
(9
5.5%
)9
(7
5.0%
)11
4 (9
4.2%
)7
(1
00.0
%)
112
(88.
9%)
33
(86.
8%)
52
(94.
5%)
8
(100
.0%
)5
(8
3.3%
%)
53
(96.
4%)
134
(8
8.2%
)N
on-C
auca
sian
15 (1
0.1%
)1
(8.3
%)
1 (2
.3%
)3
(25.
0%)
6 (5
.0%
)0
(0.0
%)
12 (9
.5%
)5
(13.
2%)
3 (5
.5%
)0
(0.0
%)
0 (0
.0%
)2
(3.6
%)
14 (9
.2%
)M
issi
ng1
(0.7
%)
2 (1
6.7%
)1
(2.3
%)
1 (0
.8%
)1
(1.6
%)
1 (2
.6%
)1
(1.8
%)
1 (1
6.7%
)1
(1.8
%)
4 (2
.6%
)
Car
diov
ascu
lar
dise
ase,
n (%
) 29
(19.
6%)
4 (3
3.3%
)9
(20.
5%)
3 (2
5.0%
)44
(36.
4%)
2 (2
8.6%
)28
(22.
2%)
17 (4
3.6%
)8
(14.
3%)
1 (1
2.5%
)1
(16.
7%)
10 (1
7.9%
)40
(26.
3%)
Coro
nary
arte
ry
dise
ase
(incl
. m
yoca
rdia
l in-
farc
tion)
17 (1
1.5%
)3
(25.
0%)
0 (0
.0%
)2
(16.
7%)
28 (2
3.1%
)1
(14.
3%)
14 (1
1.1%
)11
(28.
2%)
1 (1
.8%
)0
(0.0
%)
1 (1
6.7%
)4
(7.1
%)
20 (1
3.2%
)
Atri
al fi
brill
atio
n or
flut
ter
8 (5
.4%
)0
(0.0
%)
3 (6
.8%
)2
(16.
7%)
7 (5
.8%
)0
(0.0
%)
2 (1
.6%
)5
(12.
8%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
6 (3
.9%
)
Con
gest
ive
hear
t fa
ilure
1 (0
.7%
)1
(8.3
%)
1 (2
.3%
)1
(8.3
%)
3 (2
.5%
)0
(0.0
%)
2 (1
.6%
)1
(2.6
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
1 (0
.7%
)
Oth
er7
(4.7
%)
0 (0
.0%
)2
(4.5
%)
0 (0
.0%
)9
(7.4
%)
1 (1
4.3%
)5
(4.0
%)
3 (7
.7%
)4
(7.1
%)
0 (0
.0%
)0
(0.0
%)
3 (5
.4%
)10
(6.6
%)
Cer
ebro
vasc
ular
di
seas
e, n
(%)
26 (1
7.6%
)2
(16.
7%)
12 (2
7.3%
)3
(25.
0%)
45 (3
7.2%
)2
(28.
6%)
22 (1
7.5%
)12
(30.
8%)
11 (1
9.6%
)2
(25.
0%)
0 (0
.0%
)12
(21.
4%)
26 (1
7.1%
)
Isch
emic
stro
ke10
(6.8
%)
1 (8
.3%
)1
(2.3
%)
2 (1
6.7%
)16
(13.
2%)
0 (0
.0%
)5
(4.0
%)
6 (1
5.4%
)2
(3.6
%)
1 (1
2.5%
)0
(0.0
%)
1 (1
.8%
)4
(2.6
%)
Intra
cere
bral
ha
emor
rhag
e2
(1.4
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)2
(1.7
%)
1 (1
4.3%
)1
(0.8
%)
0 (0
.0%
)1
(1.8
%)
0 (0
.0%
)0
(0.0
%)
1 (1
.8%
)1
(0.7
%)
Uns
peci
fied
stro
ke1
(0.7
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)1
(0.8
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
1 (1
.8%
)1
(0.7
%)
TIA
9 (6
.1%
)0
(0.0
%)
1 (2
.3%
)0
(0.0
%)
15 (1
2.4%
)1
(14.
3%)
9 (7
.1%
)5
(12.
8%)
3 (5
.4%
)0
(0.0
%)
0 (0
.0%
)2
(3.6
%)
7 (4
.6%
)O
ther
5
(3.4
%)
1 (8
.3%
)5
(11.
4%)
1 (8
.3%
)9
(7.4
%)
0 (0
.0%
)2
(1.6
%)
0 (0
.0%
)3
(5.4
%)
0 (0
.0%
)0
(0.0
%)
4 (7
.1%
)7
(4.6
%)
Trau
mat
ic b
rain
in
jury
, n (%
)32
(21.
6%)
2 (1
6.7%
)13
(29.
5%)
0 (0
.0%
)26
(21.
5%)
3 (4
2.9%
)33
(26.
2%)
8 (2
0.5%
)14
(25.
0%)
2 (2
5.0%
)1
(16.
7%)
19 (3
3.9%
)38
(25.
0%)
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
301CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
TAB
LE 1
. Con
tinue
d
M
CI-
ADM
CI-
PDM
CI-
FTLD
MC
I-D
LBM
CI-
VCI
MC
I-C
AAM
CI-
DEP
MC
I-M
DM
CI-
PSY
MC
I-C
BGD
MC
I-PS
PM
CI-
Oth
erM
CI-
UN
SP
n =
148
(2
6.7%
of
tota
l)
n =
12
(2.2
%)
n =
44
(7.9
%)
n =
12
(2.2
%)
n =
121
(2
1.8%
)n
= 7
(1.3
%)
n =
126
(2
2.7%
)n
= 3
9 (7
.0%
)n
=56
(1
0.1%
)n
= 8
(1.4
%)
n =
6 (1
.1%
)n
= 5
6 (1
0.1%
)n
= 1
52
(27.
4%)
Oth
er m
edic
al
cond
ition
s, n
(%)
37 (2
5.0%
)5
(41.
7%)
28 (6
3.4%
)9
(75.
0%)
113
(93.
4%)
4 (5
7.1%
)10
0 (7
9.4%
)36
(92.
3%)
47 (8
3.9%
)8
(100
.0%
)6
(100
.0%
)43
(76.
8%)
116
(76.
3%)
Hyp
erte
nsio
n63
(42.
6%)
6 (5
0.0%
)15
(34.
1%)
5 (4
1.7%
)79
(65.
3%)
3 (4
2.9%
)69
(54.
8%)
29 (7
4.4%
)25
(44.
6%)
4 (5
0.0%
)4
(66.
7%)
18 (3
2.1%
)58
(38.
2%)
Dys
lipid
emia
56 (3
7.8%
)6
(50.
0%)
12 (2
7.3%
)4
(33.
3%)
67 (5
5.4%
)2
(28.
9%)
45 (3
5.7%
)25
(64.
1%)
17 (3
0.4%
)1
(12.
5%)
2 (3
3.3%
)14
(25.
0%)
58 (3
8.2%
)Ty
pe 2
dia
bete
s18
(12.
2%)
1 (8
.3%
)3
(6.8
%)
3 (2
5.0%
)30
(24.
5%)
0 (0
.0%
)20
(15.
9%)
10 (2
5.6%
)7
(12.
5%)
1 (1
2.5%
)0
(0.0
%)
8 (1
4.3%
)21
(13.
8%)
Oth
era
74 (5
0.0%
)2
(16.
7%)
15 (3
4.1%
)5
(41.
7%)
66 (5
4.5%
)3
(42.
9%)
62 (4
9.2%
)24
(61.
5%)
28 (5
0.0%
)3
(37.
5%)
5 (8
3.3%
)30
(53.
6%)
74 (4
8.7%
)
Neu
rolo
gica
l D
isor
ders
, n (%
)7
(58.
3%)
9 (2
0.5%
)8
(66.
7%)
34 (2
8.1%
)0
(0.0
%)
25 (1
9.8%
)9
(23.
1%)
12 (2
1.4%
)6
(75.
0%)
5 (8
3.3%
)25
(44.
6%)
35 (2
3.0%
)
Park
inso
nism
5 (3
.38%
)3
(25.
0%)
0 (0
.0%
)8
(66.
7%)
8 (6
.6%
)0
(0.0
%)
4 (3
.2%
)4
(10.
3%)
3 (5
.4%
)4
(50.
0%)
4 (6
6.7%
)5
(8.9
%)
2 (1
.3%
)Pa
rkin
son’
s dis
ease
03
(25.
0%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)1
(12.
5%)
1 (1
6.7%
)0
(0.0
%)
1 (0
.7%
)Se
izur
es/e
pile
psy
4 (2
.70%
)0
(0.0
%)
1 (2
.3%
)0
(0.0
%)
7 (5
.8%
)0
(0.0
%)
3 (2
.4%
)2
(5.1
%)
1 (1
.8%
)0
(0.0
%)
0 (0
.0%
)4
(7.1
%)
4 (2
.6%
)D
eliri
um2
(1.3
5%)
0 (0
.0%
)0
(0.0
%)
1 (8
.3%
)4
(3.3
%)
0 (0
.0%
)0
(0.0
%)
1 (2
.6%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)1
(0.7
%)
Oth
er8
(5.4
1%)
1 (8
.3%
)4
(9.1
%)
2 (1
6.7%
)18
(14.
9%)
0 (0
.0%
)13
(10.
3%)
4 (1
0.3%
)4
(7.1
4%)
2 (2
5.0%
)3
(50.
0%)
14 (2
5.0%
)15
(9.9
%)
Sens
ory
impa
irmen
t (v
isio
n, h
earin
g,
unsp
ecifi
ed),
n (%
)
40 (2
7.0%
)3
(25.
0%)
19 (4
3.2%
)2
(16.
7%)
26 (2
1.5%
)0
(0.0
%)
44 (3
4.9%
)9
(23.
1%)
16 (2
8.6%
)3
(37.
5%)
1 (1
6.7%
)12
(21.
4%)
65 (4
2.8%
)
Neu
rolo
gica
l sig
ns,
n (%
)61
(41.
2%)
6 (5
0.0%
)27
(61.
4%)
9 (7
5.0%
)44
(36.
4%)
1 (1
4.3%
)54
(42.
9%)
15 (3
8.5%
)21
(37.
5%)
8 (1
00.0
%)
6 (1
00.0
%)
28 (5
0.0%
)70
(46.
1%)
Gai
t dis
orde
r8
(5.4
%)
2 (1
6.7%
)0
(0.0
%)
3 (2
5.0%
)9
(7.4
%)
0 (0
.0%
)7
(5.6
%)
2 (5
.1%
)2
(3.6
%)
0 (0
.0%
)1
(16.
7%)
3 (5
.4%
)6
(3.9
%)
Sign
s of f
ront
al
dysf
unct
ion
9 (6
.1%
)0
(0.0
%)
8 (1
8.2%
)0
(0.0
%)
5 (5
.8%
)0
(0.0
%)
4 (3
.2%
)4
(10.
3%)
1 (1
.8%
)0
(0.0
%)
1 (1
6.7%
)3
(5.4
%)
2 (1
.3%
)
Park
inso
nism
5 (3
.4%
)4
(33.
3%)
1 (2
.3%
)5
(41.
7%)
6 (5
.0%
)0
(0.0
%)
5 (4
.0%
)4
(10.
3%)
2 (3
.6%
)6
(75.
0%)
4 (6
6.7%
)6
(10.
7%)
3 (2
.0%
)M
otor
neu
ron
sign
s1
(0.7
%)
0 (0
.0%
)1
(2.3
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
Neu
ro-
opth
alm
olog
ic
sign
s
2 (1
.4%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
1 (0
.8%
)1
(14.
3%)
0 (0
.0%
)1
(2.6
%)
0 (0
.0%
)0
(0.0
%)
1 (1
6.7%
)1
(1.8
%)
0 (0
.0%
)
Foca
l or l
ater
aliz
ing
sign
s1
(0.7
%)
0 (0
.0%
)1
(2.3
%)
0 (0
.0%
)2
(1.6
5%)
1 (1
4.3%
)1
(0.8
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
Oth
er11
(7.4
%)
0 (0
.0%
)7
(15.
9%)
1 (8
.3%
)10
(8.3
%)
0 (0
.0%
)12
(9.5
%)
3 (7
.7%
)4
(7.1
%)
0 (0
.0%
)0
(0.0
%)
8 (1
4.3%
)12
(7.9
%)
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
302CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
TAB
LE 1
. Con
tinue
d
M
CI-
ADM
CI-
PDM
CI-
FTLD
MC
I-D
LBM
CI-
VCI
MC
I-C
AAM
CI-
DEP
MC
I-M
DM
CI-
PSY
MC
I-C
BGD
MC
I-PS
PM
CI-
Oth
erM
CI-
UN
SP
n =
148
(2
6.7%
of
tota
l)
n =
12
(2.2
%)
n =
44
(7.9
%)
n =
12
(2.2
%)
n =
121
(2
1.8%
)n
= 7
(1.3
%)
n =
126
(2
2.7%
)n
= 3
9 (7
.0%
)n
=56
(1
0.1%
)n
= 8
(1.4
%)
n =
6 (1
.1%
)n
= 5
6 (1
0.1%
)n
= 1
52
(27.
4%)
Psyc
hiat
ric d
isor
ders
, n
(%)
108
(73.
0%)
8 (6
6.7%
)27
(61.
4%)
6 (5
0.0%
)74
(61.
2%)
2 (2
8.6%
)11
0 (9
0.9%
)31
(79.
5%)
45 (8
0.4%
)4
(50.
0%)
4 (6
6.7%
)34
(60.
7%)
94 (6
1.8%
)
Moo
d di
sord
ers
40 (2
7.0%
)6
(50.
0%)
12 (2
7.3%
)4
(33.
3%)
42 (3
4.7%
)1
(14.
3%)
90 (7
1.4%
)13
(33.
3%)
34 (6
0.7%
)2
(25.
0%)
2 (3
3.3%
)16
(28.
6%)
51 (3
3.6%
)A
nxie
ty d
isor
ders
14 (9
.5%
)1
(8.3
%)
6 (1
3.6%
)1
(8.3
%)
14 (1
1.6%
)1
(14.
3%)
35 (2
7.8%
)6
(15.
4%)
19 (3
3.9%
)0
(0.0
%)
0 (0
.0%
)6
(10.
7%)
19 (1
2.5%
)Ps
ycho
tic d
isor
ders
1 (0
.7%
)0
(0.0
%)
0 (0
.0%
)1
(8.3
%)
1 (0
.8%
)0
(0.0
%)
3 (2
.4%
)3
(7.7
%)
2 (3
.6%
)0
(0.0
%)
0 (0
.0%
)0
(0.0
%)
1 (0
.7%
)A
lcoh
ol a
nd o
ther
su
bsta
nce
use/
abus
e
25 (1
6.9%
)0
(0.0
%)
6 (1
3.6%
)5
(41.
7%)
51 (4
2.1%
)5
(71.
4%)
27 (2
1.4%
)32
(82.
1%)
8 (1
4.3%
)0
(0.0
%)
2 (3
3.3%
)5
(8.9
%)
2 (1
.3%
)
Oth
er
neur
opsy
chia
tric
sym
ptom
s (in
clud
ing
PTSD
)
4 (2
.7%
)0
(0.0
%)
1 (2
.3%
)1
(8.3
%)
3 (2
.5%
)0
(0.0
%)
6 (4
.8%
)4
(10.
3%)
2 (3
.6%
)0
(0.0
%)
1 (1
6.7%
)2
(3.6
%)
2 (1
.3%
)
GD
S-15
3.
52 (2
.96)
5.33
(3.6
4)3.
21 (2
.67)
6.44
(2.1
7)4.
11 (2
.83)
1.8
(1.3
6)7
(2.9
0)4.
13 (2
.91)
6.10
(3.1
6)6.
33 (2
.0)
7.0
(2.4
)5.
29 (2
.96)
3.49
(2.1
4)
Dep
ress
ion
seve
rity,
n
(%)
Non
e80
(54.
1%)
4 (4
0.0%
)30
(78.
9%)
2 (1
6.7%
)56
(62.
9%)
4 (5
7.1%
)37
(30.
1%)
16 (6
9.6%
)17
(35.
4%)
1 (1
6.7%
)1
(20.
0%)
25 (4
6.3%
)10
2 (6
8.0%
)M
ild24
(16.
2%)
4 (4
0.0%
)3
(7.9
%)
5 (4
1.7%
)22
(24.
7%)
1 (1
4.3%
)47
(38.
2%)
4 (1
7.4%
)19
(39.
6%)
3 (5
0.0%
)1
(20.
0%)
20 (3
7.0%
)33
(22.
0%)
Mod
erat
e4
(2.7
%)
2 (2
0.0%
)3
(7.9
%)
2 (1
6.7%
)6
(6.7
%)
0 (0
.0%
)25
(20.
3%)
1 (4
.3%
)7
(14.
6%)
2 (3
3.3%
)3
(60.
0%)
7 (1
3.0%
)12
(8.0
%)
Seve
re4
(2.7
%)
0 (0
.0%
)2
(5.3
%)
0 (0
.0%
)5
(5.6
%)
0 (0
.0%
)14
(11.
4%)
2 (8
.7%
)5
(10.
4%)
0 (0
.0%
)0
(0.0
%)
2 (3
.7%
)3
(2.0
%)
MM
SE25
.79
(3.2
5)27
.56
(2.7
0)24
.92
(4.2
2)25
.18
(2.5
3)26
.74
(2.1
7)27
.17
(1
.17)
26.9
9 (2
.49)
25.0
9 (2
.80)
26.3
1 (3
.41)
26.7
5
(1.3
1)25
.50
(3
.17)
27.6
7 (1
.86)
27.4
3
(1.6
9)
MoC
A
19.9
0 (3
.85)
24.2
5 (3
.65)
20.8
0 (4
.02)
22.2
2 (4
.25)
21.0
6 (2
.72)
20.7
1
(1.5
5)21
.97
(2.8
8)19
.69
(3.0
5)21
.73
(3.6
3)21
.50
(2
.50)
20.0
0
(2.8
0)22
.35
(2.9
4)21
.98
(3
.13)
Not
e. A
pro
porti
on o
f PR
OM
PT c
linic
pat
ient
s may
hav
e m
ultip
le h
ealth
and
/or p
sych
iatri
c co
nditi
ons.
Ther
efor
e, th
e nu
mbe
r of p
erce
ntag
es re
flect
s the
pro
porti
on b
etw
een
the
num
ber o
f par
ticip
ants
with
the
cond
ition
and
the
tota
l sam
ple
size
for e
ach
of th
e M
CI e
tiolo
gy su
bgro
ups.
AD
= A
lzhe
imer
’s d
isea
se; P
D =
Par
kins
on’s
dis
ease
; FTL
D =
Fro
ntot
empo
ral l
obar
deg
ener
atio
n; D
LB =
Dem
entia
with
Lew
y bo
dies
; VC
I = V
ascu
lar C
ogni
tive
Impa
irmen
t; C
AA
= C
ereb
ral a
myl
oid
angi
opat
hy;
DEP
= D
epre
ssiv
e sy
mpt
oms r
elat
ed c
ogni
tive
impa
irmen
t; M
D =
Mix
ed d
emen
tia; P
SY =
Psy
chia
tric
cond
ition
s, no
t inc
ludi
ng d
epre
ssio
n; C
BG
D =
Cor
ticob
asal
gan
glio
nic
dege
nera
tion;
PSP
= P
rogr
essi
ve
supr
anuc
lear
pal
sy; O
ther
= D
ue to
syst
emic
, nut
ritio
nal,
or o
ther
neu
rolo
gica
l cau
ses,
such
as t
raum
atic
bra
in in
jury
, can
cer o
r can
cer t
reat
men
t, et
c.; U
NSP
= U
nspe
cifie
d; P
TSD
= P
ost-t
raum
atic
stre
ss d
isor
der;
TIA
= T
rans
ient
isch
emic
atta
ck; G
DS-
15 =
15-
Item
Ger
iatri
c de
pres
sion
scal
e; M
MSE
= M
ini-m
enta
l Sta
tus E
xam
; MoC
A =
Mon
treal
cog
nitiv
e as
sess
men
ta T
he “
Oth
er”
cate
gory
in th
e ot
her m
edic
al c
ondi
tions
incl
udes
med
ical
con
ditio
ns su
ch a
s hyp
othy
roid
ism
, res
pira
tory
dis
orde
rs, o
steo
poro
sis,
and
med
ical
pro
cedu
res.
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
303CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
be associated with lower health-care literacy,(56) health-care access and utilization,(57) and research participation.(58) The eligibility criteria of language fluency may further limit the number of ethnic minority participants in MCI research stud-ies. Calgary is relatively homogenous, with visible minorities accounting for 33.7% of the population(59) (comparatively, Toronto’s population has 51.1% visible minorities(60)). Thus, both samples in this study were less ethnically diverse than anticipated.
Our central finding is that MCI participants with psy-chiatric, medical, and neurological conditions were regularly excluded from Canadian MCI research studies, despite these conditions being clinically prevalent. Psychiatric disorders, TBI, and sensory impairment were particularly common-place in PROMPT (83% MCI-PD patients had ≥1), but these
FIGURE 1. Search strategy for the systematic review
conditions were systematic exclusion criteria from > 80% studies in the systematic review. Psychiatric disorders are prevalent among older adults(61-65) and can impact dementia risk and related outcomes.(66-70) The presence of neuropsychi-atric symptoms in MCI doubles progression rate to dementia.(71) Cross-sectionally, it is difficult to know whether psychi-atric symptoms are a risk factor or a prodrome of dementia.(72) However, large prospective cohorts have demonstrated a linkage between age of onset of psychiatric symptomatology and incident dementia,(73-75) and mild behavioural impair-ment (MBI, i.e., later life onset of sustained neuropsychiatric symptoms of any severity(76-79)) is an at-risk state for incident cognitive decline and dementia.(80-83) Thus, excluding MCI research participants based on scores above cut-off on a cross-sectional neuropsychiatric measure may inadvertently exclude
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
304CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
TABLE 2. Sample and health characteristics of MCI-AD participants
PROMPT Registry Systematic Review t/χ2 df p 95% CI Cohen’s d/hn = 148 n = 4881
Sociodemographic Characteristics
Age, years 68.61 (9.47) 73.75 (6.98) 8.67 4778 < .001 [-6.30, -3.97] 0.62Sex, n (%)
Female 60 (40.5%) 2032(53.7%)a 9.9 1 0.002 [4.97, 20.96] 0.26Male 87 (59.2%) 1746 (46.1%) 9.17 1 0.002 [4.46, 20.50] 0.25
Education, years 13.74 (3.97) 12.90 (3.61)b 2.53 4162 0.01 [0.19, 1.49] 0.22Race, n (%)
Caucasian 132 (89.2%)c 198 (93.8%)d 0.88 1 0.35 [-2.82, 8.85] 0.15Non-Caucasian 15 (10.1%) 11 (5.2%) 3.11 1 0.08 [-0.59, 11.29] 0.19
Health CharacteristicsCardiovascular disease, n (%) 29 (19.6%) 46 (26.6%)e 2.18 1 0.14 [-2.33, 15.99] 0.16
Coronary artery disease (incl. myocardial infarction) 17 (11.5%) 27 (15.6%) 1.14 1 0.29 [-0.59, 11.29] 0.12
Atrial fibrillation or flutter 8 (5.4%) 9 (5.2%) 0.01 1 0.93 [-3.58, 11.56] 0.003Congestive heart failure 1 (0.7%) 2 (1.2%) 0.2 1 0.66 [-2.69, 3.49] 0.05Other 7 (4.7%) 8 (4.6%) 0 1 0.96 [-3.17, 6.08] 1.06
Cerebrovascular disease, n (%) 26 (17.6%) 14 (9.9%)f 3.58 1 0.06 [-0.33, 15.66] 0.23Ischemic stroke/transient
ischemic attack 17 (11.5%) 14 (9.9%) 0.19 1 0.66 [-5.75, 8.88] 0.05
Intracerebral haemorrhage 2 (1.4%) n/aUnspecified stroke 1 (0.7%) n/aOther 5 (3.4%) n/a
Traumatic brain injury, n (%) 32 (21.6%) n/aOther medical conditions, n (%) g
Hypertension 63 (42.6%) 103 (56.3%) 6.13 1 0.01 [2.87, 24.08] 0.28Dyslipidemia 56 (37.8%) 21 (11.5%) 31.8 1 <.001 [17.17, 35.26] 0.63Type 2 diabetes 18 (12.2%) 31 (16.9%) 1.48 1 0.22 [-3.06, 12.26] 0.14Other 74 (50.0%) 37 (20.2%) 32.5 1 <.001 [19.57, 37.27] 0.64
Neurological Disorders, n (%) 22 (14.86%) n/aParkinsonism 5 (3.38%) n/aParkinson’s disease 0 n/aSeizures/epilepsy 4 (2.70%) n/aDelirium 2 (1.35%) n/aOther 8 (5.41%) n/a
Sensory impairment (vision, hearing, unspecified), n (%) 40 (27.0%) n/a
Neurological signs, n (%) 61 (41.2%) n/aGait disorder 8 (5.4%) n/aSigns of frontal dysfunction 9 (6.1%) n/aParkinsonism 5 (3.4%) n/aMotor neuron signs 1 (0.7%) n/aNeuro-opthalmologic signs 2 (1.4%) n/aFocal or lateralizing signs 1 (0.7%) n/aOther 11 (7.4%) n/a
Psychiatric disorders, n (%) 108 (73.0%) n/aMood disorders 40 (27.0%) n/aAnxiety disorders 14 (9.5%) n/aPsychotic disorders 1 (0.7%) n/aAlcohol and other substance use/abuse 25 (16.9%) n/aOther neuropsychiatric symptoms
(including PTSD) 4 (2.7%) n/a
GDS-15 3.52 (2.96) 3.47 (2.97) h 0.09 150 0.92 [-1.03, 1.13] 0.02
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
305CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
TABLE 2. Continued
PROMPT Registry Systematic Review t/χ2 df p 95% CI Cohen’s d/hn = 148 n = 4881
Psychiatric disorders, n (%) (continued)
Depression severity, n (%)None 80 (54.1%) 989 (80.2%) i 40.7 1 <.001 [16.82, 35.50] 0.57Mild 24 (16.2%) 245 (19.9%) 0.87 1 0.35 [-4.55, 9.77] 0.09Moderate 4 (2.7%) 0 (0.0%)Severe 4 (2.7%) 0 (0.0%)
Cognitive Characteristics
MMSE 25.79 (3.25) 27.44 (1.04)j 20.5 4344 < .001 [-1.81, -1.50] 0.68MoCA 19.90 (3.85) 23.40 (0.57)k 27.9 1255 < .001 [-3.74, -3.25] 1.27
n/a = Medical, neurological, and psychiatric conditions were either excluded or not reported; Other = medical conditions included conditions such as respiratory disorders, osteoporosis, cancer, and medical procedures. aTwenty articles did not report sex distribution (1096 missing cases).bThirteen articles did not report years of education information (623 missing cases). Two articles reported education levels in categorical variables (n = 226).cOne MCI-AD case did not report race/ethnicity information.dFive articles reported race/ethnicity, wherein majority of the samples were Caucasian, with percentages ranging from 67.57% to 100% of the sample (n = 211). eTotal number of participants with cardiovascular diseases in the literature. Three articles reported participants with cardiovascular diseases (n = 173). Percentage reflects the proportion between the number of participants with cardiovascular disease and the total sample size of all the studies reported cardiovascular disease.fTotal number of participants with a history of stroke/transient ischemic attack reported in the literature. Two articles reported participants with cerebrovascular diseases (n = 141). Percentage reflects the proportion between the number of participants with a history of stroke/transient ischemic attack and the total sample size of all the studies reported cerebrovascular events.gThree studies reported multiple medical conditions (n = 183). Subsequent percentage reflects the proportion between the number of participants with the specific medical condition and the total sample size of all studies reported other category of the other medical condition.hThree articles used GDS-15 to report research participants’ depressive symptoms (n = 40)iThirty articles used self-report measures to assess depressive symptoms (n = 1234), other than the GDS-15. Percentage represents the proportion between the number of participants in each severity category based on established cut-off scores and the total sample size of all the articles with depressive symptoms questionnaires.jNinety-three articles used MMSE and two articles used standardized MMSE (SMMSE) to assess general cognition (n = 4224). Scores of MMSE and SMSSE are comparable.kThirty articles used MoCA to assess general cognition (n = 1150).
those with prodromal disease, diluting the sample. The data on MBI can inform the approach to psychiatric conditions in MCI, and including those with MBI may, in fact, enrich the MCI sample for prodromal dementia.
Sensory impairment is common in late life(84-88) and is associated with increased risk of MCI(89) and dementia,(90-93) especially multisensory impairment.(94) Sensory impairment may even serve as a potential biomarker for pathological cognitive aging.(95) Similarly, TBI is another identified risk factor for MCI(96-98) and dementia,(99,100) and is associated with neurodegenerative protein pathology.(101,102) The presence of chronic, systemic health conditions can also exacerbate cogni-tive decline.(103-107) Given that chronic health conditions and sensory impairments are highly prevalent among Canadian seniors(7,84,85,108) and older adults are at high risk of sustain-ing a TBI,(109,110) the exclusion of these comorbidities may further undermine the representativeness of MCI samples and research findings. Predictably, these comorbidities were accompanied by between-sample discrepancies in cognitive performance in this study—clinic patients performed ap-proximately two points lower on MMSE and MoCA testing compared to research participants. The magnitude of study effects is likely to be over- or underestimated in MCI research
participants who are overall healthier with less cognitive impairment relative to current real-world patient populations. It is additionally possible that healthier, less cognitive im-paired individuals self-select into research protocols, further reducing generalizability. Canadian practitioners seeking to implement evidence-based care should carefully consider the characteristics of relevant research samples before applying results derived from them in their practice.
The search terms used in the systematic review were selected to best match the criteria used to diagnose patients in PROMPT. As such, some important Canadian studies of cog-nitive impairment, no dementia (CIND) or vascular cognitive impairment (VCI)(111) were not captured, such as the Canadian Study of Health and Aging (CSHA),(112) the Canadian Collab-orative Cohort of Related Dementias (ACCORD),(113) and the Consortium to Investigate Vascular Impairment of Cognition (CIVIC).(111) The concepts underlying CIND are considerably different from Petersen’s(27) and NIA-AA’s(18) conceptualiza-tion of MCI, as CIND encompasses non-neurodegenerative and not necessarily progressive causes of cognitive impair-ment(114) (including psychiatric, neurodevelopmental and toxic).(113) Nonetheless, these studies offer similar insights to the present work. ACCORD(113) and CIVIC(111) were carried
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TABLE 3. Sample and health characteristics of MCI-PD participants
PROMPT Registryn = 12
Systematic Reviewa
n = 100t/χ2 df p 95% CI Cohen’s
d/h
Sociodemographic Characteristics
Age, years 66.94 (6.28) 66.45 (6.87) 0.24 110 .81 [-3.64, 4.62] 0.07
Sex, n (%)
Female 2 (16.7%) 29 (35.4%)b 1.67 1 .20 [-10.74, 34.15] 0.43Male 10 (83.3%) 53 (64.6%) 1.64 1 .20 [-10.99, 34.82] 0.43
Education, years 17.67 (4.23) 13.88 (3.49) 3.07 107 .003 [1.34, 6.24] 0.98
Race/Ethnicity, n (%)Caucasian 9 (90.0%)c 22 (100%)d
Non-Caucasian 1 (10.0%)
Health Characteristics
Cardiovascular disease, n (%) 4 (33.3%) n/aCoronary artery disease 3 (25.0%) n/aAtrial fibrillation or flutter 0 (0.0%) n/aCongestive heart failure 1 (8.3%) n/aOther 0 (0.0%) n/a
Cerebrovascular disease, n (%) 2 (16.7%) n/aIschemic stroke 1 (8.3%) n/aIntracerebral haemorrhage 0 (0.0%) n/aUnspecified stroke 0 (0.0%) n/aOther 1 (8.3%) n/a
Traumatic brain injury, n (%) 2 (16.7%) n/a
Other medical conditions, n (%)Hypertension 6 (50.0%) n/aDyslipidemia 6 (50.0%) n/aType 2 diabetes 1 (8.3%) n/aOthere 2 (16.7%) n/a
Neurological Disorders, n (%) 7 (58.3%) n/aParkinsonism 3 (25.0%) n/aParkinson’s disease 3 (25.0%) n/aSeizures/epilepsy 0 (0.0%) n/aDelirium 0 (0.0%) n/aOther 1 (8.3%) n/a
Sensory impairment (vision, hearing, unspecified), n (%)
3 (25.0%) n/a
Neurological Signs 6 (50.0%) n/aGait disorder 2 (16.7%) n/aSigns of frontal dysfunction 0 (0.0%) n/aParkinsonism 4 (33.3%) n/aMotor neuron signs 0 (0.0%) n/aNeuro-opthalmologic signs 0 (0.0%) n/aFocal or lateralizing signs 0 (0.0%) n/aOther 0 (0.0%) n/a
out in Canadian dementia clinics and, like PROMPT, partici-pants frequently had medical and psychiatric comorbidities. CSHA(112) also documented depression (8.0%), psychiatric conditions (6.6%), and substance abuse (8.3%) as common contributors to cognitive decline. Average MMSE scores in ACCORD(113) were similar to those in PROMPT (M = 26.9, SD = 3.0), while those in CIVIC(111) were lower (M = 21.9, SD = 6.2). The differences in the MMSE scores between
PROMPT and CIVIC patients may be attributable to the fact that they were a decade older, on average, than PROMPT patients and may have had more severe neurological damage (e.g., stroke).
Our results highlight the diverse presumed neuropatho-logical etiologies of MCI in clinical practice, which is not reflected in the Canadian research literature. The vast majority (95%) of identified published studies focused on MCI due to
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307CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
TABLE 3. Continued
PROMPT Registryn = 12
Systematic Reviewa
n = 100t/χ2 df p 95% CI Cohen’s
d/h
Psychiatric disorders, n (%) 8 (66.7%) n/aMood disorders 6 (50.0%) n/aAnxiety disorders 1 (8.3%) n/aPsychotic disorders 0 (0.0%) n/aAlcohol and other substance use/abuse 0 (0.0%) n/aOther neuropsychiatric symptoms (including PTSD)
0 (0.0%) n/a
GDS-15 5.33 (3.64) n/aDepression severity, n (%)
None 4 (40.0%) 47 (100.0%)f 30.97 1 <.001 [30.29,83.18] 1.77Mild 4 (40.0%) 0 (0.0%) 19.86 1 <.001 [15.62,68.73] 1.37Moderate 2 (20.0%) 0 (0.0%) 9.57 1 .002 [3.80, 50.98] 0.93Severe 0 (0.0%) 0 (0.0%) 0 0 1 [0.0, 0.0]
Cognitive CharacteristicsMMSE 27.56 (2.70) 28.07 (1.23)g 0.93 50 .36 [-1.61, 0.59] 0.24
MoCA 24.25 (3.65) 25.82 (2.02)h 2.06 69 .04 [-3.09, -0.05] 0.53
n/a = Medical, neurological, and psychiatric conditions were either excluded or not reported.aTwo studies did not report any inclusion/exclusion criteria or any medical or psychiatric comorbidities. Four studies provided inclusion/exclusion criteria based on current or history of systemic or psychiatric illnesses (see Appendix A). bOne article did not report sex distribution (18 missing cases).cTwo MCI-PD cases did not report race information.dOne article reported race/ethnicity, wherein 100% of sample was Caucasians (n = 22).eThe “Other” category of other medical conditions included Meniere’s disease, arthritis, and hypothyroidism.fDepression severity frequency was determined based on published severity cut-off scores of the average total scores of the Hamilton Depression Rating Scale (HAM-D) or the Beck Depression Inventory-II (BDI-II) found in three articles, n = 47.gTwo Studies used MMSE to measure general cognition, n = 40.hFour articles used MoCA to measure general cognition, n = 60.
AD, conceptualized as cognitive impairment primarily af-fecting memory not better accounted for by other neurologic insults. In the PROMPT sample, however, only about a quarter of patients were thought to have pure AD as the cause for MCI. Many more cases were presumed to have a vascular etiological basis in whole or in part, as well as a large number of other conditions. These results, together with the broader findings of multiple comorbidities in our clinical sample, support our initial hypothesis that memory clinic patients are considerably more diverse in many respects than those included in research studies.
Strengths and Limitations
This study represents an important first step in evaluating the real-word representativeness of participants with MCI in Canadian research protocols, and demonstrates key differ-ences between characteristics of memory clinic patients and research samples. Our clinical MCI cohort was fairly large and diverse, and considered generally representative of the MCI clientele served in Calgary. However, it represented a convenience sample that is likely to differ from other Can-adian MCI cohorts, and findings may not be generalizable to clinics in other parts of Canada and elsewhere. Our findings may also not be generalizable to population-based samples of person with MCI. Other limitations include the fact that
we only examined cognitive performance on the MMSE and MoCA tests; a more comprehensive neuropsychological battery could provide more information about relevant dif-ferences between clinic and research samples. Nevertheless, findings highlight the importance of interpreting MMSE and MoCA scores together with patients’ medical and psychiatric history. While we attempted to ensure sample independence in the systematic review, certain participants may have ended up in multiple studies, which could have inflated between-group differences. Moreover, multiple comparison tests may have inflated Type I error rates. Therefore, results should be interpreted with caution; however, substantial effect sizes were found for the aforementioned comparison tests, sug-gesting practical significance. The accuracy of the etiological diagnoses assigned to the MCI cases in PROMPT cannot be guaranteed, nor can those of patients included in the studies within the systematic review. In PROMPT, routine clinical protocols for determination of presumed etiology did not include AD biomarker testing, which is currently recom-mended in Canada for research only,(115) or neuropathological confirmation. The prevalence of mixed or multiple etiologies was also likely underestimated. Further, we did not examine differences between sub-types of MCI-AD (amnestic vs. non-amnestic). Given that MCI-PD patients are often seen at movement disorders clinics, patients with this form of MCI
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308CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
were likely underrepresented in the current study. We were unable to examine the MCI-VCI subpopulation, considering this group was underrepresented in the MCI research studies identified in the literature, despite vascular disease being a common contributor to cognitive impairment. Lastly, findings may not be generalizable to non-Caucasian groups. Despite these limitations, given its relatively large and diverse clinic sample, the current study serves as an important initial step in demonstrating key demographic and clinical differences among MCI memory clinic patients and research participants in Canada.
ACKNOWLEDGEMENTS
The authors recognize financial support from the University of Waterloo (Research Chair to CJM), and the Canada Research Chairs Program (Tier II CRC to BLC).
CONFLICT OF INTEREST DISCLOSURES
The authors declare that no conflicts of interest exist.
APPENDICES
Appendix A. Weighted mean and pooled standard deviation calculationThe weighted mean is a form of average. However, instead of each data point contributing equally to the final average (i.e., an arithmetic mean), some data points contribute more to the final average than others. The weighted mean is calculated by multiplying each data point by the weight, and then dividing it by the sum of all the weights. The weighted mean in the current systematic review was calculated by multiplying the mean scores in each study (i.e., age, years of education, and the MMSE and MoCA scores) by each study’s sample size (i.e., the weight). This was then divided by the sum of the sample sizes in all studies. See the weighted mean formula below:
x = mean; w = sample size
The pooled standard deviation is the weighted average of standard deviations. The pooled standard deviation was calculated by: 1) subtracting 1 from each sample size; 2) then multiply the value by the sample variance (i.e., squaring the standard deviation) and sum the multiplied value for all studies; 3) dividing the results from the first two steps by the overall sample size minus the total number of studies; and 4) taking the square root of the weighted variance terms. See the pooled standard deviation formula below:
For studies that reported median, range, or interquartile range, the mean and standard deviations were estimated via an online calculator (http://www.comp.hkbu.edu.hk/~xwan/median2mean.html). Specifically, if the range of a score was provided in an article, the standard deviation of the sample was estimated using methods proposed by Hozo et al.(1) If the arti-cle presented only median and interquartile range, the mean of the sample was estimated using methods proposed by Luo and colleagues,(2) and the standard deviation was estimated using methods proposed by Wan and colleagues.(3)
REFERENCES
1. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5(1); Article number 13. Avail-able from: https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/1471-2288-5-13
2. Luo D, Wan X, Liu J, et al. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res. 2018;27(6):1785–805. Available from: https://journals.sagepub.com/doi/abs/ 10.1177/0962280216669183
3. Wan X, Wang W, Liu J, et al. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14(1); Article number 135. Available from: https://link.springer.com/article/10.1186/1471-2288-14-135.
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309CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
App
endi
x B
. Arti
cles
reta
ined
in th
e sy
stem
atic
revi
ew
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icle
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ovin
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iagn
ostic
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rite
ria
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SEM
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Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
Kaba
ni et
al.(2
8)Qu
ébec
15M
= 7
7.4,
SD
= 5
.8F:
8
(53.
33%
) M
: 7
(46.
67%
)
Peter
sen(1
16)
M =
27.
73Ob
serv
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men
tion
of ex
clusio
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iteria
Mas
soud
et
al.(1
17)
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94
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D-10
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Pros
pect
coho
rtEx
clusio
n: S
erio
us ch
roni
c med
ical i
llnes
s or c
ance
r, CV
D, cl
inica
l, lab
orato
ry w
ork
or n
euro
imag
ing
data
sugg
estiv
e of a
noth
er ca
use f
or d
emen
tia, u
se o
f ps
ycho
activ
e dru
gs, c
orre
cted
cent
ral a
cuity
< 2
0/50
, and
in
abili
ty to
per
form
at le
ast 2
tests
/pro
cedu
res
Wha
tmou
gh et
al.
(119
)Qu
ébec
16M
= 7
4.5,
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= 9
.1F:
4 (2
5%)
M: 1
2 (7
5%)
M =
13,
SD
= 3.
9Pe
terse
n(120
)M
= 2
7.2,
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.7Ob
serv
.Ex
clusio
n: B
lood
wor
k co
nfirm
ed tr
eatab
le ill
ness
es
Berli
n et
al.(1
21)
Québ
ec10
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= 7
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Peter
sen(1
22)
M =
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9,
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Obse
rv.
Exclu
sion:
Med
ical o
r neu
rolo
gica
l con
ditio
ns th
at ex
plain
the c
ogni
tive d
eclin
e
Chan
tal et
al.(1
23)
Québ
ec14
M =
69.
2,
SD =
6.8
F: 5
(3
5.71
%)
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(6
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M =
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Peter
sen(1
24)
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Obse
rv.
Exclu
sion:
Cur
rent
use
of c
ogni
tive e
nhan
cer,
curre
nt o
r pa
st sy
stem
ic (in
cl. ty
pe 2
diab
etes)
or p
sych
iatric
illn
ess
or T
BI th
at m
ay af
fect
cogn
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func
tion
Phill
ips e
t al.(2
9)Qu
ébec
16M
= 7
5.8,
SD
= 6
.4 F
: 4 (2
5%)
M: 1
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5%)
M =
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4,
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3.6
Peter
sen(1
22)
M =
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6,
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Obse
rv.
No m
entio
n of
exclu
sion
crite
ria
Gesla
ni et
al.(1
25)
Ontar
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.07,
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=
7.72
F: 3
6 (6
3.16
%)
M: 2
1 (3
6.84
%)
M =
12.
67,
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3.2
4Pe
terse
n(122
)M
=26
.58,
SD
= 2
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Obse
rv.
Exclu
sion:
Mus
t be fl
uent
in E
nglis
h, h
ave a
dequ
ate
hear
ing
and
visio
n to
com
plete
testi
ng, a
ny n
euro
logi
cal
cond
ition
that
may
caus
e mem
ory
impa
irmen
t, DS
M-
III-R
crite
ria fo
r dem
entia
, evi
denc
e of c
hron
ic alc
ohol
or
oth
er d
rug
abus
e, str
oke h
ypox
ia, in
tracr
anial
mas
s les
ions
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es, b
rain
trau
ma
Levi
noff
et al.
(126
) Qu
ébec
34M
= 7
4.1,
SD
= 7
.1M
= 1
0.5,
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= 3
.6Pe
terse
n(122
) M
= 2
7.7,
SD
= 2
.1Ob
serv
.Ex
clusio
n: A
dditi
onal
neur
olog
ical d
isord
ers t
hat
inter
fere
with
nor
mal
cogn
itive
func
tioni
ng, s
tructu
ral
brain
dise
ases
confi
rmed
by
CT an
d/or
MRI
Belle
ville
et
al.(1
27)
Québ
ec28
M =
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.33,
SD
= 7
.3
M =
14.
6,
SD =
5Pe
terse
n(128
)M
=28
.94,
SD
= 1
.2GD
S: M
=
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SD
= 3.
8
N-ra
nd
feas
ibil
Exclu
sion:
Unc
orre
cted
visio
n or
hea
ring
impa
irmen
t, us
e of p
sych
otro
pic m
edica
tions
kno
wn to
impa
ir co
gniti
on, p
hysic
al m
obili
ty o
r man
ual d
exter
ity
impa
irmen
t, in
tellec
tual
defic
iency
, alco
holis
m o
r to
xico
man
ia, p
rese
nce o
r hist
ory
of se
vere
psy
chiat
ry
diso
rder
, cer
ebro
vasc
ular
diso
rder
s, ne
urol
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sord
er, g
ener
al an
esth
esia
in th
e pas
t 6 m
onth
s
Duon
g et
al.(1
29)
Québ
ec61
M =
74
.68,
SD
=
6.48
M =
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3,
SD =
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9Ch
ertk
ow et
al.
(130
)M
= 2
7.2,
SD
= 2
.25
Obse
rv.
Exclu
sion:
Pre
senc
e of a
ny m
edica
l, ne
urol
ogica
l, or
ps
ychi
atric
expl
anati
on fo
r mem
ory
loss
, exc
ept f
or
mild
dep
ress
ion
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
310CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
Hudo
n et
al.(1
31)
Québ
ec14
M =
66.
6,
SD =
11
.9
F: 11
(7
8.57
%)
M: 3
(2
1.43
%)
M =
13.
9,
SD =
3.6
Peter
sen(2
7)M
= 2
8.1,
SD
= 1
.5Ob
serv
.Ex
clusio
n: H
istor
y of
TBI
, stro
ke o
r tra
nsito
ry ce
rebr
al isc
hem
ia, fo
rmer
intra
cran
ial su
rger
y, ne
urol
ogica
l di
sord
er o
f cer
ebra
l orig
inal
or as
socia
ted w
ith an
othe
r fo
rm o
f dem
entia
, sig
nific
ant p
sych
iatric
illn
ess,
signi
fican
t vas
cular
risk
facto
rs, al
coho
lism
/dru
g ad
dicti
on o
r exc
essiv
e alco
hol c
onsu
mpt
ion
base
d on
DS
M-IV
, and
gen
eral
anes
thes
ia in
the p
ast 1
2 m
onth
s
Levi
noff
et al.
(34)
Québ
ec73
M =
74,
SD
= 7
.3M
= 1
2.7,
SD
= 3
.4Pe
terse
n(132
)M
= 2
7.7,
SD
= 1
.9Ob
serv
.No
men
tion
of ex
clusio
n cr
iteria
Mur
phy
et al.
(133
)On
tario
33M
= 7
6.6,
SD
= 5
.4F:
16
(48.
48%
) M
: 17
(51.
52%
)
M =
13.
9,
SD =
3.6
Peter
sen(2
7)M
= 2
7.8,
SD
= 1
.4Ob
serv
.Ex
clusio
n: M
edica
l or p
sych
iatric
illn
ess t
hat m
ay
cont
ribut
e to
cogn
itive
dec
line.
Sing
h et
al.(3
5)Qu
ébec
65M
= 7
5,
SD =
6F:
34
(52.
31%
) M
: 26
(47.
69%
)
Peter
sen(1
28)
M =
26.
9,
SD =
2.5
Obse
rv.
No m
entio
n of
exclu
sion
crite
ria
Belle
ville
et
al.(1
34)
Québ
ec25
M =
64
.76,
SD
=
10.8
3
F: 1
4 (5
6%) M
: 11
(44%
)
M =
14.
32,
SD =
4.7
1Pe
terse
n(135
)M
=28
.36,
SD
= 1
.98
Obse
rv.
Exclu
sion:
Non
-am
nesti
c MCI
subt
ypes
, alco
hol
abus
e, pr
esen
ce o
r hist
ory
of se
vere
psy
chiat
ric
diso
rder
, int
ellec
tual
defic
iency
, GDS
scor
es >
17,
CV
D, n
euro
logi
cal d
isord
er, s
ystem
ic di
seas
es k
now
to
cont
ribut
e to
cogn
itive
impa
irmen
t, ge
nera
l ane
sthes
ia in
the l
ast 6
mon
ths,
signi
fican
t im
pairm
ent o
f han
d m
obili
ty, an
d un
corre
cted
hear
ing
and
visio
n
Stan
dish
et al
.(42)
Ontar
io16
6Pe
terse
n(128
) SM
MSE
: M
= 27
.1, S
D =
2.30
Cros
s- se
ctEx
clusio
n: P
artic
ipan
ts ab
le to
com
mun
icate
in E
nglis
h,
and
thos
e with
GDS
scor
es >
7
Babi
ns et
al.(1
36)
Québ
ec82
M =
74
.85,
SD
=
6.04
M =
11.2
, SD
= 3
.43
Peter
sen(1
22)
M =
27.2
1,
SD =
1.8
4Ob
serv
.In
clusio
n: P
artic
ipan
ts ha
d no
evid
ence
of s
ystem
ic or
ne
urol
ogica
l dise
ase t
hat m
ay af
fect
cogn
itive
func
tion
Exclu
sion:
Stru
ctura
l bra
in d
iseas
e con
firm
ed b
y co
mpu
ted to
mog
raph
y an
d/or
mag
netic
reso
nanc
e im
agin
g
Belle
ville
etal.
(137
)Qu
ébec
20M
= 6
6.3,
SD
=
10.9
F: 1
2 (6
0%) M
: 8
(40%
)
M =
13.
9,
SD =
5Pe
terse
n(135
)M
=28
.15,
SD
= 2
.1Ob
serv
.Ex
clusio
n: N
on-a
mne
stic M
CI, c
urre
nt o
r a h
istor
y of
alco
holis
m, s
ever
e psy
chiat
ric d
isord
er, s
igni
fican
t ce
rebr
ovas
cular
diso
rder
, neu
rolo
gica
l diso
rder
, in
tellec
tual
defic
iency
, sys
temic
dise
ase k
nown
to im
pair
cogn
ition
, gen
eral
anae
sthes
ia in
the p
ast 6
mon
ths,
signi
fican
t im
pairm
ent o
f han
d m
obili
ty
Clém
ent e
t al.(1
38)
Québ
ec68
M =
69
.06,
SD
=
7.89
M =
13.
88,
SD =
4.3
4Pe
terse
n(122
) M
=27
.96,
SD
= 1
.76
GDS-
5: M
=
1.09
, SD
= 1.
18
Obse
rv.
Exclu
sion:
Pre
senc
e of a
ny si
gnifi
cant
syste
mic,
ne
urol
ogica
l, or
psy
chiat
ric il
lnes
ses t
hat m
ay ex
plain
co
gniti
ve im
pairm
ent
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
311CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
Djor
djev
ic et
al.(1
39)
Québ
ec51
M =
75.
4,
SD =
6.
75
F: 2
6 (5
0.98
%)
M: 2
5 (4
9.02
%)
M =
11.5
Cher
tkow
et
al.(1
30)
M =
27.
26GD
S: M
=
6.12
Obse
rv.
Exclu
sion:
Pre
senc
e of n
euro
logi
cal,
psyc
hiatr
ic, o
r ot
her m
edica
l fac
tors
that
may
affe
ct ol
facti
on
Fello
ws et
al.(1
40)
Québ
ec90
M =
73.
7,
SD =
8.2
F: 4
5 (5
0%) M
: 45
(50%
)
M =
10.
7,
SD =
3.5
Peter
sen
(116
,122
)M
= 2
7.5,
SD
= 1
.9Pr
ospe
ct lo
ngEx
clusio
n: M
ajor d
epre
ssio
n vi
a <16
on
the G
DS,
syste
mic
or o
ther
neu
rolo
gica
l dise
ase t
hat m
ay in
terfe
re
with
cogn
itive
func
tion,
stru
ctura
l bra
in d
iseas
e
Houd
e et a
l.(36)
Qu
ébec
60M
= 7
4.5,
SD
= 6
.5F:
31
(51.
67%
) M
: 29
(48.
33%
)
M =
10.
5,
SD =
3.1
Peter
sen(1
28)
M =
27.
2,
SD =
1.9
GDS:
M =
10
.4, S
D =
5.7
Obse
rv.
No m
entio
n of
exclu
sion
crite
ria
Mur
phy
et al.
(141
)On
tario
17M
= 7
6.2,
SD
= 5
.7F:
10
(58.
82%
) M
: 7
(41.
18%
)
M =
14.
5,
SD =
2.8
Peter
sen(2
7)M
= 2
7.3,
SD
= 2
Obse
rv.
Exclu
sion:
Med
ical o
r psy
chiat
ric co
nditi
ons t
hat
may
acco
unt f
or m
emor
y de
cline
, oth
er th
an p
ossib
le in
cipien
t AD
(thro
ugh
med
ical h
istor
y re
view
and
curre
nt se
lf-re
port
moo
d sta
tus v
ia th
e GDS
or H
ADS)
Troy
er et
al.(1
42)
Ontar
io29
M =
75.
1,
SD =
7F:
16
(55.
17%
) M
: 13
(44.
83%
)
M =
14.
3,
SD =
2.6
Peter
sen(2
7)M
= 2
7.8,
SD
= 1
.7Ob
serv
.Ex
clusio
n: M
edica
l or p
sych
iatric
dise
ase t
hat m
ay
acco
unt f
or m
emor
y im
pairm
ent
Troy
er et
al.(1
43)
Ontar
io68
M =
75.
4,
SD =
6.8
F: 3
6 (5
2.94
%)
M: 3
2 (4
7.06
%)
M =
14.
5,
SD =
3.3
Peter
sen(2
7)
M =
27.
7 1.
7, S
D =
HADS
- De
pres
sion:
M
= 9
.1, S
D =
5.9
Rand
om
cont
rol t
rial
(RCT
)
Exclu
sion:
Med
ical o
r psy
chiat
ric co
nditi
on th
at m
ay
acco
unt f
or m
emor
y im
pairm
ent
Bélan
ger &
Be
llevi
lle(1
44)
Québ
ec18
Peter
sen(1
35)
M =
27.
3,
SD =
1.8
Obse
rv.
Exclu
sion:
Pre
senc
e of a
ny si
gnifi
cant
syste
mic,
ne
urol
ogica
l, or
psy
chiat
ric co
nditi
on th
at m
ay
cont
ribut
e to
cogn
itive
impa
irmen
t
Bram
bati
et al.
(145
)Qu
ébec
25M
=
73.4
4,
SD =
7.
05
F: 1
7 (6
8%) M
: 8
(22%
)
M =
13.
21,
SD =
4.6
6Pe
terse
n(128
) M
=27
.38,
SD
= 1
.53
Obse
rv.
Exclu
sion:
Hist
ory
of sy
stem
ic or
neu
rolo
gica
l dise
ase
inclu
ding
cere
brov
ascu
lar d
iseas
e, pa
st or
curre
nt
psyc
hiatr
ic ill
ness
, TBI
, for
mer
intra
cran
ial su
rger
y, hi
story
of a
lcoho
lism
or d
rug
abus
e, un
treate
d m
edica
l or
meta
bolic
cond
ition
, gen
eral
anes
thes
ia in
the l
ast 1
2 m
onth
s, un
corre
cted
hear
ing
and
visio
n pr
oblem
s
Burto
n et
al.(1
46)
BC92
M =
79
.21,
SD
=
5.31
M =
13.
29
SD =
2.8
0W
inbl
ad et
al.(1
47)
M =
28.4
5,
SD =
1.3
4Cr
oss-s
ect
data
extra
c lo
ng
Exclu
sion:
Diag
nosis
of d
emen
tia, h
istor
y of
sign
ifica
nt
head
inju
ry, o
ther
neu
rolo
gica
l or m
ajor m
edica
l ill
ness
es (e
.g.,
hear
t dise
ase,
canc
er, a
nd P
D), s
ever
e se
nsor
y im
pairm
ent,
exten
sive s
ubsta
nce a
buse
, cur
rent
ps
ychi
atric
diag
nose
s or u
se o
f psy
chot
ropi
c dru
gs
Clém
ent e
t al.(1
48)
Québ
ec10
M =
67.
2,
SD =
8.
03
F: 7
(70%
) M
: 3
(30%
)
M =
13.
7,
SD =
3.8
Peter
sen(1
22)
M =
27.
6,
SD =
1.6
5GD
S-15
: M
= 3.
29, S
D =
2.98
Obse
rv.
Exclu
sion:
Pre
senc
e of a
ny si
gnifi
cant
med
ical,
neur
olog
ical,
or p
sych
iatric
cond
ition
that
may
expl
ain
cogn
itive
impa
irmen
t
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
312CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
Clém
ent e
t al.(1
49)
Québ
ec30
M =
65
.97,
SD
=
10.4
3
F: 1
6 (5
3.33
%)
M: 1
4 (4
6.67
%)
M =
14.
5,
SD =
4.6
6Pe
terse
n(128
) M
=28
.63,
SD
= 1
.16
Obse
rv.
Exclu
sion:
A d
iagno
sis o
f pro
babl
e AD
and
othe
r fo
rms o
f dem
entia
, hist
ory
of n
euro
logi
cal o
r sev
ere
psyc
hiatr
ic di
sord
er, c
ardi
ovas
cular
dise
ase,
alcoh
olism
, dr
ug ad
dicti
on, u
sing
psyc
hoac
tive d
rug
or g
ener
al an
esth
esia
in th
e pas
t 6 m
onth
s
Hudo
n et
al.(1
50)
Québ
ec20
M =
66.
1,
SD =
7.6
F: 9
(45%
) M
: 11
(55%
)
M =
14.
6,
SD =
4.2
Peter
sen(2
7)M
= 2
7.9,
SD
= 1
.8GD
S-5:
M
= 1.
1, S
D =
1.3
Obse
rv.
Exclu
sion:
hist
ory
of T
BI, s
troke
or t
rans
itory
cere
bral
ische
mia,
form
er in
tracr
anial
surg
ery,
histo
ry o
f ne
urol
ogica
l diso
rder
of c
ereb
ral o
rigin
or a
ssoc
iated
wi
th an
othe
r for
m o
f dem
entia
(e.g
., M
S, p
arki
nson
ism,
front
otem
pora
l dem
entia
), hi
story
or c
urre
nt p
sych
iatric
ill
ness
es b
ased
on
DSM
-IV cr
iteria
, alco
holis
m/d
rug
addi
ction
acco
rdin
g to
DSM
-IV cr
iteria
, uns
table
meta
bolic
or m
edica
l con
ditio
n, g
ener
al an
esth
esia
in th
e pa
st 12
mon
ths
Mon
tero-
Odas
so
et al.
(151
) On
tario
11M
= 7
6.6,
SD
= 7
.3F:
6
(54.
55%
) M
: 5
(45.
45%
)
M =
14.
1,
SD =
3.4
Peter
sen(1
22)
M =
287
SD
= 1.
6M
= 2
2.8
SD =
1.2
Obse
rv.
Exclu
sion:
Any
gait
diso
rder
, inc
ludi
ng P
D, p
revi
ous
strok
e, cli
nica
l oste
oarth
ritis
in lo
wer l
imbs
join
ts,
myo
path
y, or
neu
ropa
thy,
pres
ence
of d
epre
ssiv
e sy
mpt
oms (
≥ 5
/15
on th
e GDS
)
Mon
tero-
Odas
so
et al.
(152
)On
tario
55M
= 7
7.7,
SD
=
5.89
F: 2
5 (4
5.45
%)
M: 3
0 (5
4.55
%)
M =
12.
1,
SD =
3.4
Peter
sen(1
28)
M =
26.
8,
SD =
2.1
M =
22.
4,
SD =
3.2
Ob
serv
.Ex
clusio
n: A
n ob
jectiv
e gait
diso
rder
due
to P
D,
prev
ious
stro
ke, c
linica
l oste
oarth
ritis
in lo
wer l
imb
join
ts, m
yopa
thy,
or n
euro
path
y, de
pres
sive s
ympt
oms
( ≥5/
15 o
n th
e GDS
)
Taler
et al
.(37)
Québ
ec20
M =
75.
8,
SD =
7.
62
F: 1
0 (5
0%) M
: 10
(50%
)
M =
12.
45,
SD =
2.7
2Pe
terse
n(122
) M
=27
.36,
SD
= 2
.27
Obse
rv.
No m
entio
n of
exclu
sion
crite
ria
Ville
neuv
e et
al.(1
53)
Québ
ec68
M =
70
.65,
SD
=
8.66
F: 3
9 (5
7.35
%)
M: 2
9 (4
2.65
%)
Cauc
asian
: 68
(100
%)
M =
14.
51,
SD =
4.4
Peter
sen(1
54)
M =
27.5
3,
SD =
2.2
Obse
rv.
Exclu
sion:
Gen
eral
anes
thes
ia in
the p
ast 6
mon
ths,
histo
ry o
f neu
rolo
gica
l dise
ase o
r eve
nt (i
.e., s
troke
, PD
, epi
lepsy
, bra
in an
oxia)
, psy
chiat
ric d
isord
er
(schi
zoph
reni
a, M
DD, a
lcoho
lism
), or
TBI
Arse
naul
t-La
pier
re et
al.
(155
)
Québ
ec42
M =
76.
2,
SD =
7.2
F: 1
8 (4
2.86
%)
M: 2
4 (5
7.14
%)
M =
10.
9,
SD =
3.2
Peter
sen(1
24)
M =
26.
7,
SD =
2.1
GDS:
M
= 6.
9, S
D =
5.6
Obse
rv.
Exclu
sion:
Rev
ersib
le ca
uses
of c
ogni
tive i
mpa
irmen
t
Bélan
ger e
t al.
(156
) Qu
ébec
20M
= 7
2.7,
SD
= 6
.8M
= 1
3.6,
SD
= 4
Peter
sen(1
35)
M =
27.
4,
SD =
2.1
GDS:
M =
1,
SD
= 1
Obse
rv.
Exclu
sion:
Any
sign
ifica
nt sy
stem
ic, n
euro
logi
cal
or p
sych
iatric
cond
ition
s tha
t may
cont
ribut
e to
cogn
itive
impa
irmen
t
Clém
ent &
Be
llevi
lle(1
57)
Québ
ec26
M =
67
.85,
SD
=
8.71
F: 1
5 (5
7.69
%)
M: 1
1 (4
2.31
%)
M =
14.
47,
SD =
3.9
5Pe
terse
n (1
20,1
24,1
47)
M =
27.6
6,
SD =
1.6
0Ob
serv
.Ex
clusio
n: P
rese
nce o
f any
sign
ifica
nt sy
stem
ic,
neur
olog
ical,
or p
sych
iatric
cond
ition
s tha
t may
af
fect
cogn
ition
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
313CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
Clém
ent e
t al.(1
58)
Québ
ec12
M =
67
.83,
SD
=
7.49
F: 9
(75%
) M
: 3
(25%
)
M =
13.
25,
SD =
3.9
6Pe
terse
n(1
22,1
28,1
47)
M =
27.8
3,
SD =
1.5
9Ob
serv
.Ex
clusio
n: P
rese
nce o
f any
med
ical,
neur
olog
ical o
r ps
ychi
atric
illne
sses
that
may
cont
ribut
e to
cogn
itive
im
pairm
ent
Jean
et al
.(159
) Qu
ébec
22M
=
68.5
5,
SD =
7.
89
F: 1
3 (5
9.09
%)
M: 9
(4
0.91
%)
M =
14.
5,
SD =
3.8
6Pe
terse
n (2
7,12
8)
M =
29.
5,
SD =
0.7
0RC
TEx
clusio
n: M
eetin
g diag
nosti
c crit
eria
for a
ny de
men
tia,
any n
euro
logi
cal o
r sys
temic
prob
lem kn
own t
o im
pair
cogn
ition
, cur
rent
or pa
st alc
ohol
or dr
ug ab
use,
chro
nic p
sych
iatric
illn
ess o
r an a
cute
episo
de of
MDD
, ps
ycho
tropi
c or o
ther
med
itatio
n kno
w to
affe
ct co
gniti
on
(incl.
chol
ines
teras
e inh
ibito
r/cog
nitio
n enh
ance
r)
Joub
ert e
t al.(1
60)
Québ
ec15
M =
73.
7,
SD =
6.3
F: 8
(5
3.33
%)
M: 7
(4
6.67
%)
M =
12.
8,
SD =
4.8
Peter
sen(1
35)
M =
27.
4,
SD =
1.6
Obse
rv.
Exclu
sion:
A h
istor
y of
syste
mic
or n
euro
logi
cal
dise
ases
(inc
l. ce
rebr
ovas
cular
dise
ase,
past
or cu
rrent
ps
ychi
atric
illne
ss, T
BI, h
istor
y of
alco
holis
m, u
ntre
ated
med
ical o
r meta
bolic
cond
ition
), ge
nera
l ane
sthes
ia in
th
e pas
t 12
mon
ths,
or u
ncor
recte
d he
arin
g or
visi
on
impa
irmen
t
McL
augh
lin et
al.
(161
) On
tario
21M
=
74.0
1,
SD =
6.
22
F: 9
(4
2.86
%)
M: 1
2 (5
7.14
%)
M =
12.
15,
SD =
2.5
4Pe
terse
n(27)
M =
27.2
1,
SD =
2.6
6Ob
serv
.Ex
clusio
n: F
luen
t in
Engl
ish, u
ncor
recte
d vi
sion,
pr
esen
ce o
f neu
rolo
gica
l or p
sych
iatric
illn
ess,
strok
e, he
ad in
jury
, alco
hol o
r dru
g ab
use,
and
depr
essio
n
Mon
tero-
Odas
so
& M
uir(1
62)
Ontar
io43
M =
75.
1,
SD =
6.3
F: 2
3 (5
3.49
%)
M: 2
0 (4
6.51
%)
M =
12.
7,
SD =
3.3
Win
blad
et al
.(147
)M
= 3
.64,
SD
=0.
89Ob
serv
.Ex
clusio
n: In
abili
ty to
und
ersta
nd E
nglis
h,
Park
inso
nism
, use
of a
ny p
sych
otro
pic m
edica
tion,
or
diag
nosis
of d
epre
ssio
n
Sylv
ain-R
oy et
al.
(163
) Qu
ébec
20M
= 6
4.4,
SD
=
11.5
F: 1
3 (6
5%) M
: 7
(35%
)
M =
14,
SD
= 4.
7Pe
terse
n(128
) M
= 2
8, S
D =
2.1
Obse
rv.
Exclu
sion:
Unc
orre
cted v
ision
or he
arin
g im
pairm
ent,
pres
ence
or hi
story
of al
coho
lism
, sev
ere p
sych
iatric
di
sord
er, si
gnifi
cant
cere
brov
ascu
lar di
sord
er, ne
urol
ogica
l di
sord
er, in
tellec
tual
defic
iency
, pre
senc
e of s
ystem
ic ill
ness
es th
at af
fect
cogn
ition
, gen
eral
anes
thes
ia in
the
past
6 mon
ths,
impa
irmen
t han
d mot
orici
ty
Arse
naul
t-La
pier
re et
al.
(164
)
Québ
ec39
M =
72.
5,
SD =
8.6
F: 2
2 (5
6.41
%)
M: 1
7 (4
3.59
%)
M =
13,
SD
= 3
Peter
sen(1
24)
M =
28.
1,
SD =
1.5
GDS:
M =
6;
SD
= 3.
9Ob
serv
.Ex
clusio
n: S
erio
us h
ealth
pro
blem
or s
ystem
ic ca
use
or o
ther
neu
rolo
gica
l illn
esse
s tha
t cou
ld ac
coun
t for
co
gniti
ve im
pairm
ent o
r chr
onic
psyc
hiatr
ic di
sord
er
(oth
er th
an d
epre
ssio
n)
Belle
ville
et
al.(1
65)
Québ
ec15
M =
70
.13,
SD
=
7.34
F: 11
(7
3.33
%)
M: 4
(2
6.67
%)
M =
13.
73,
SD =
4.3
3Pe
terse
n(128
)M
=27
.73,
SD
= 1
.87
Non-
rand
om
train
ing
Exclu
sion:
Unc
orre
cted
visio
n an
d he
arin
g, p
roba
ble o
r po
ssib
le AD
, oth
er fo
rms o
f dem
entia
, cur
rent
or h
istor
y of
seve
re p
sych
iatric
diso
rder
, cer
ebro
vasc
ular
dise
ase,
neur
olog
ical d
isord
er o
r alco
holis
m, g
ener
al an
esth
esia
in th
e pas
t 6 m
onth
s, us
e of p
sych
otro
pic m
edica
tion,
pr
esen
ce o
f MRI
exclu
sion
crite
ria
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
314CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
Belle
ville
et
al.(1
66)
Québ
ec28
M =
70.
9,
SD =
6.5
M =
13.
7,
SD =
3.8
Peter
sen(1
35)
M =
27.
8,
SD =
1.4
Obse
rv.
Exclu
sion:
Alco
hol o
r sub
stanc
e add
ictio
n, p
rese
nce
of h
istor
y of
seve
re p
sych
iatric
diso
rder
(i.e.
, MDD
or
schi
zoph
reni
a), d
yslex
ia, in
tellec
tual
defic
iency
, sig
nific
ant c
ereb
ral d
isord
er, n
euro
logi
cal d
isord
er,
gene
ral a
nesth
esia
in th
e las
t 6 m
onth
s, us
e of
med
icatio
n kn
own
to af
fect
mem
ory,
indi
vidu
als w
ith
signi
fican
t mus
ical e
xper
tise
Brun
et et
al.(1
67)
Québ
ec33
M =
72
.83,
SD
=
7.52
F: 1
6 (4
8.48
%)
M: 1
7 (5
1.52
%)
M =
13.
00,
SD =
5.11
Peter
sen(2
7)M
=23.
33, S
D =
2.7
GDS:
M =
9.
15, S
D =
2.87
Obse
rv.
Exclu
sion:
A h
istor
y of
neu
rolo
gica
l dise
ase,
inclu
ding
ce
rebr
ovas
cular
dise
ase,
past
or cu
rrent
psy
chiat
ric
diso
rder
s oth
er th
an m
ajor d
epre
ssio
n, T
BI, a
lcoho
lism
, un
treate
d m
edica
l or m
etabo
lic co
nditi
on, g
ener
al an
esth
esia
in th
e pas
t 12
mon
ths,
ECT
in th
e pas
t 12
mon
ths,
form
er in
tracr
anial
surg
ery,
unco
rrecte
d he
arin
g an
d vi
sion
prob
lems
Gagn
on &
Be
llevi
lle(1
68)
Québ
ec20
M =
73.
4,
SD =
6.
89
M =
15.
9,
SD =
4.1
Gaut
hier
et al
.(169
) M
=27
.95,
SD
= 1
.5Ob
serv
.Ex
clusio
n: A
lcoho
lism
, gen
eral
anes
thes
ia in
the p
ast
6 m
onth
s, pr
esen
ce o
f hist
ory
of se
vere
psy
chiat
ric
diso
rder
s, ne
urol
ogica
l diso
rder
s, ce
rebr
ovas
cular
di
sord
er o
r stro
ke
Gao
et al.
(170
) On
tario
23M
= 7
0.2,
SD
= 6
.8F:
10
(43.
48%
) M
: 13
(56.
52%
)
M =
14.
3,
SD =
3.2
Peter
sen(1
22)
M =
27.
3,
SD =
2.4
Obse
rv.
Exclu
sion:
Sec
onda
ry ca
uses
of d
emen
tia, c
omor
bid
neur
olog
ical o
r psy
chiat
ric il
lnes
s
Hudo
n et
al.(1
71)
Québ
ec23
M =
66.
8,
SD =
8.8
F: 9
(3
9.13
%)
M: 1
4 (6
0.87
%)
M =
14.
6,
SD =
4.2
Peter
sen(2
7)M
= 2
7.7,
SD
= 2
GDS-
5: M
=
1.1,
SD
= 1.
4
Obse
rv.
Exclu
sion:
Hist
ory
of T
BI, s
troke
or t
rans
itory
cere
bral
ische
mia,
form
er in
tracr
anial
surg
ery,
neur
olog
ical
diso
rder
of c
ereb
ral o
rigin
al or
oth
er d
emen
tia (e
.g.,
MS,
pa
rkin
soni
sm, f
ront
otem
pora
l dem
entia
), ps
ychi
atric
illne
ss, c
urre
nt o
r hist
ory
of al
coho
lism
or d
rug
addi
ction
, uns
table
meta
bolic
or m
edica
l con
ditio
n,
gene
ral a
nesth
esia
in th
e pas
t 6 m
onth
s
Matt
eau
et al.
(172
) Qu
ébec
22M
= 7
0,
SD =
6.8
F: 1
2 (5
4.55
%)
M: 1
0 (4
5.45
%)
M =
13.
7,
SD =
4.4
Peter
sen
(27,
147)
M
= 2
8.8,
SD
= 1
.8HA
MD:
M
= 4.
3, S
D =
3.5
Obse
rv.
Exclu
sion:
acut
e epi
sode
of M
DD d
eterm
ined
by
HAM
D (sc
ores
> 1
3), a
ny n
euro
logi
cal o
r sys
temic
prob
lem o
ther
than
PD
and A
D kn
own
to af
fect
cogn
ition
(e.g
., TB
I, tu
mor
), de
ep b
rain
stim
ulati
on o
r ot
her b
rain
neu
rosu
rger
y, cu
rrent
or p
ast a
lcoho
l or d
rug
abus
e, ch
roni
c psy
chiat
ric il
lnes
s
Mui
r et a
l.(173
) On
tario
29M
= 7
3.6,
SD
= 6
.2F:
17
(58.
62%
) M
: 12
(41.
38%
)
M =
11.9
, SD
= 2
.9W
inbl
ad et
al.(1
47)
M =
27.
5,
SD =
1.9
M =
23.
4,
SD =
2.8
Obse
rv.
Exclu
sion:
Inab
ility
to u
nder
stand
Eng
lish,
falls
in th
e pa
st ye
ar, P
arki
nson
ism o
r oth
er n
euro
logi
cal d
isord
er
with
resid
ual d
eficit
s, m
uscu
losk
eletal
diso
rder
affe
cting
ga
it pe
rform
ance
, use
of p
sych
otro
pic m
edica
tion,
and
MDD
Prot
zner
et al
.(174
) On
tario
14M
= 6
8.6,
SD
= 7
.4F:
7 (5
0%)
M: 7
(5
0%)
M =
13.
4,
SD =
2.8
Peter
sen(1
28)
M =
27.
7,
SD =
1.1
Obse
rv.
Exclu
sion:
Sec
onda
ry ca
uses
of M
CI (i
.e., v
ascu
lar,
meta
bolic
, nut
ritio
nal,
or m
ood
diso
rder
s)
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
315CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
Rups
ingh
et
al.(1
75)
Ontar
io12
M =
71.
8,
SD =
9.9
F: 5
(4
1.67
%)
M: 7
(5
8.33
%)
M =
18,
SD
= 5.
4Pe
terse
n(128
) M
= 2
7.6,
SD
= 1
.9Ob
serv
.Ex
clusio
n: C
ontra
indi
catio
ns to
MRI
, clin
ical
depr
essio
n, su
bstan
ce ab
use,
diag
nosis
of o
ther
de
men
tia o
r pre
senc
e of s
igni
fican
t vas
cular
dise
ase o
r ce
rebr
ovas
cular
infa
rcts
Sher
win
et al.
(176
) Qu
ébec
28M
=
75.9
3,
SD =
6.
55
M: 2
8 (1
00%
)M
= 11
.63,
SD
= 4
.33
Peter
sen(1
22)
M =
27.4
6,
SD =
2.2
2RC
TEx
clusio
n: U
ncon
trolle
d hy
perte
nsio
n, ab
norm
al clo
tting
, hyp
erco
agul
able
states
, slee
p ap
nea,
carc
inom
a of
the p
rosta
te, h
yper
calce
mia,
meta
bolic
dise
ase,
seve
re C
OPD,
rena
l ins
uffic
iency
, liv
er d
iseas
e, un
stabl
e co
rona
ry ar
tery
dise
ase,
histo
ry o
f cer
ebro
vasc
ular
ac
ciden
t, re
cent
clas
sical
mig
rain
es, t
hrom
boph
lebiti
s or
thro
mbo
embo
lic d
iseas
e, cu
rrent
ly ta
king
Cou
mad
in
anti-
diab
etic m
edica
tions
, cho
lines
teras
e inh
ibito
rs or
oth
er co
gniti
ve en
hanc
er m
edica
tions
(e.g
., gi
ngko
bi
loba
, vita
min
E)
Vand
erm
orris
et
al.(1
77)
BC77
Cauc
asian
: 77
(100
%)
Win
blad
et al
.(147
) M
= 2
8.6,
SD
= 1
.3Pr
ospe
ct lo
ngEx
clusio
n: D
iagno
sed
dem
entia
or M
MSE
<24
, a
histo
ry o
f sig
nific
ant h
ead
inju
ry (l
oss o
f con
scio
usne
ss
>5),
othe
r neu
rolo
gica
l or m
ajor m
edica
l illn
esse
s, se
vere
sens
ory
impa
irmen
t, alc
ohol
or s
ubsta
nce a
buse
, cu
rrent
psy
chiat
ric d
iagno
sis, p
sych
otro
pic d
rug
use,
and
not fl
uent
in E
nglis
h
Ville
neuv
e et
al.(1
78)
Québ
ec44
M =
72
.67,
SD
=
7.19
F: 2
3 (5
2.27
%)
M: 2
1 (4
7.73
%)
M =
13.
6,
SD =
5.1
4Pe
terse
n(154
) M
=27
.66,
SD
= 1
.72
Obse
rv.
Exclu
sion:
Dem
entia
, hist
ory
of te
mpo
ral l
obe e
pilep
sy
or o
ther
neu
rolo
gica
l diso
rder
s (PD
), alc
ohol
ism, m
ajor
psyc
hiatr
ic di
seas
e, pr
esen
ce o
f a st
roke
or l
arge
ves
sel
dise
ase,
histo
ry o
f stro
ke, T
BI, g
ener
al an
esth
esia
in th
e pa
st 6
mon
ths.
Xie e
t al.(4
3)Qu
ébec
187
M =
80,
SD
= 6
F: 1
01
(54.
01%
) M
: 86
(45.
99%
)
≤ 12
yea
rs:
n =
56; >
12
yea
rs:
n =
80; 5
1 m
issin
g ca
ses
Peter
sen
(27,
122)
M =
26.
6,
SD =
2Ob
serv
.Ex
clusio
n: P
artic
ipan
ts wi
th le
ss th
an 2
MM
SE sc
ores
Arse
naul
t-Lap
i-er
re et
al.(1
79)
Québ
ec60
M =
75,
SD
= 7
M =
11.2
, SD
= 3
.1Pe
terse
n(120
) M
= 2
7.1,
SD
= 2
.2GD
S: M
=
6.7,
SD
= 4.
9
Obse
rv.
Exclu
sion:
Rev
ersib
le ca
uses
of c
ogni
tive d
ysfu
nctio
n
Arse
naul
t-Lap
i-er
re et
al.(1
80)
Québ
ec21
M =
77.
1,
SD =
1.3
F: 7
(3
3.33
%)
M: 1
4 (6
6.67
%)
M =
15.
9,
SD =
1.0
Peter
sen(1
24)
M =
27.
8,
SD =
2M
= 2
3.5,
SD
= 0
.7Ob
serv
.Ex
clusio
n: M
edica
l or p
sych
iatric
diso
rder
that
may
ac
coun
t for
cogn
itive
impa
irmen
t
Barn
abe e
t al.(3
8)Qu
ébec
20M
= 7
6.4,
SD
=
6.87
F: 8
(40%
) M
: 12
(60%
)
M =
14.
6,
SD =
4.3
Peter
sen
(27,
122)
M =
28.3
5,
SD =
1.4
6Ob
serv
.No
men
tion
of ex
clusio
n cr
iteria
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
316CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
Bram
bati
et al.
(39)
Qu
ébec
13M
= 7
2.7,
SD
= 4
.9F:
7
(53.
85%
) M
: 6
(46.
15%
)
M =
14.
8,
SD =
3.9
Peter
sen(1
22)
M =
28.
7,
SD =
1.1
GDS:
M
= 3.
6, S
D =
2.3
Obse
rv.
No m
entio
n of
exclu
sion
crite
ria
Clém
ent &
Be
llevi
lle(1
81)
Québ
ec26
M =
67
.85,
SD
=
8.70
F: 1
5 (5
7.69
%)
M: 1
1 (4
2.31
%)
M =
14.
47,
SD =
3.9
5Pe
terse
n(122
,128
,147
)M
=27
.66,
SD
= 1
.60
Obse
rv.
Exclu
sion:
Any
sign
ifica
nt m
edica
l, ne
urol
ogica
l, or
ps
ychi
atric
cond
ition
s tha
t may
cont
ribut
e to
cogn
itive
di
fficu
lties
Gagn
on &
Be
llevi
lle(1
82)
Québ
ec24
M =
67
.71,
SD
=
7.12
M =
14.
04,
SD =
5.2
8Pe
terse
n(122
)M
=27
.96,
SD
= 1
.35
GDS:
M =
3.
34, S
D =
2.25
RCT
Exclu
sion:
alco
holis
m, g
ener
al an
aesth
esia
in th
e pas
t 6
mon
ths,
pres
ence
or h
istor
y of
seve
re p
sych
iatric
diso
r-de
rs, T
BI, d
epre
ssio
n, n
euro
logi
cal d
isord
ers,
or st
roke
, de
men
tia
Mor
in et
al.(1
83)
Québ
ec12
M =
71.
2,
SD =
6.
19
F: 6
(50%
) M
: 6
(50%
)
M =
14.
65,
SD =
5.5
5Pe
terse
n(27)
M =
23.
6,
SD =
3.53
GDS:
M =
8,
SD =
1.7
9Ob
serv
.Ex
clusio
n: H
istor
y of
TBI
, pre
senc
e of s
igni
fican
t va
scul
ar ri
sk, f
orm
er in
tracr
anial
surg
ery,
neur
olog
ical
diso
rder
(e.g
., de
men
tia, M
S, p
arki
nson
ism,
front
otem
pora
l dem
entia
); un
stabl
e meta
bolic
or
med
ical c
ondi
tion
(e.g
., un
cont
rolle
d di
abete
s, hy
poth
yroi
dism
), ge
nera
l ane
sthes
ia in
the p
ast 1
2 m
onth
s, co
ntra
indi
catio
n fo
r MRI
, pas
t or c
urre
nt
diag
nosis
of M
DD
Rain
ville
et
al.(1
84)
Québ
ec81
M =
69
.83,
SD
=
8.20
M =
14.
65,
SD =
4.1
6Pe
terse
n(135
)M
=,2
7.74
SD
= 1
.65
GDS:
M =
3.
47, S
D =
2.93
Obse
rv.
Exclu
sion:
alco
holis
m, p
rese
nce o
r hist
ory
of se
vere
ps
ychi
atric
diso
rder
, neu
rolo
gica
l diso
rder
or s
troke
, ge
nera
l ane
sthes
ia in
the p
ast 6
mon
ths,
and
MDD
Troy
er et
al.(1
85)
Ontar
io24
M =
76.
1,
SD =
7.6
F: 1
5 (6
2.5%
) M
: 6
(37.
5%)
M =
14.
2,
SD =
2.5
Knop
man
et
al.(1
86)
M =
27.
4,
SD =
1.8
HADS
-De
pres
sion:
M
= 3
, SD
= 2.
6
Obse
rv.
Exclu
sion:
Med
ical o
r psy
chiat
ric co
nditi
ons t
hat m
ay
acco
unt f
or m
emor
y im
pairm
ent
Ville
neuv
e &
Belle
ville
(187
) Qu
ébec
49M
= 7
1.6,
SD
= 7
.1F:
25
(51.
02%
) M
: 24
(48.
98%
)
M =
13.
3,
SD =
4.9
Peter
sen(1
54)
M =
27.
8,
SD =
1.6
Obse
rv.
Exclu
sion:
Dem
entia
, alco
holis
m, p
rese
nce o
f a st
roke
or
larg
e ves
sel d
iseas
e on
the M
RI, h
istor
y of
stro
ke,
TBI,
and
gene
ral a
nesth
esia
in th
e pas
t 6 m
onth
s
Ansa
do et
al.(1
88)
Québ
ec11
M =
73.
7,
SD =
6.3
F: 5
(4
5.45
%)
M: 6
(5
4.55
%)
M =
12.
8,
SD =
4.8
Peter
sen(1
28)
M =
27.
4,
SD =
1.6
Obse
rv.
Exclu
sion:
Hist
ory
of sy
stem
ic or
neu
rolo
gica
l dise
ase,
past
or cu
rrent
psy
chiat
ric il
lnes
s, TB
I, hi
story
of
alcoh
olism
, unt
reate
d m
edica
l or m
etabo
lic co
nditi
on,
gene
ral a
nesth
esia
in th
e pas
t 12
mon
ths,
unco
rrecte
d he
arin
g or
visi
on p
robl
ems
Clém
ent e
t al.(1
89)
Québ
ec24
M =
68
.42,
SD
=
9.27
F: 1
4 (5
8.33
%)
M: 1
0 (4
1.67
%)
M =
14.
5,
SD =
4.1
7Pe
terse
n(122
,128
,147
)M
=27
.96,
SD
=1.
78Ob
serv
.Ex
clusio
n: A
ny si
gnifi
cant
syste
mic,
neu
rolo
gica
l or
psyc
hiatr
ic co
nditi
on th
at m
ay co
ntrib
ute t
o co
gniti
ve
impa
irmen
t
Gu et
al.(4
4)
Ontar
io20
M =
66
.95
M =
15
(n
= 17
)NI
A-AA
(18)
M
= 2
8.25
Obse
rv.
Exclu
sion:
Rev
ersib
le ca
uses
of d
emen
tia (T
SH, B
12,
folat
e defi
cienc
y)
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
317CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
Kons
ztowi
cz et
al.
(46)
Québ
ec19
M =
78
.21,
SD
=
6.34
F: 1
0 (5
2.63
%)
M: 9
(4
7.37
%)
M =
11.1
6,
SD =
6.1
6Pe
terse
n(122
)M
=26
.79,
SD
= 2
.54
M=2
0.79
, SD
=3.
68GD
S: M
=
2.63
, SD
= 1.
89
Rand
fe
asib
ilEx
clusio
n: In
abili
ty to
com
ply
with
trea
tmen
t pro
gram
du
e to
signi
fican
t com
orbi
d ill
ness
or a
n an
ticip
ated
inab
ility
to at
tend
all st
udy
sess
ions
Guild
et al
.(190
) On
tario
14M
=
73.0
7,
SD =
6.
44
F: 1
2 (8
5.71
%)
M: 2
(1
4.29
%)
M =
14.
57,
SD =
1.8
3Pe
terse
n(124
)M
=28
.14,
SD
= 1
.46
Obse
rv.
Exclu
sion:
Lea
rned
Eng
lish
after
the a
ge o
f 5,
psyc
hiatr
ic or
med
ical c
ondi
tion
that
may
acco
unt f
or
mem
ory
impa
irmen
t (i.e
., pr
ior h
istor
y of
neu
rolo
gica
l di
sord
er, h
ead
inju
ry, d
emen
tia, s
troke
), he
art a
ttack
, di
abete
s, an
xiety
, or p
sych
iatric
diso
rder
, nor
mal
or
cont
rolle
d ch
oles
terol
and
thyr
oid
func
tion
Julay
anon
t et
al.(1
91)
Québ
ec16
5M
=
73.9
4,
SD =
0.
88
F: 1
07
(64.
85%
) M
: 58
(35.
15%
)
M =
10.
53,
SD =
0.4
5Pe
terse
n(122
)M
=20.
18,
SD =
0.3
Retro
char
t re
view
Exclu
sion:
Mod
erate
to se
vere
whi
te m
atter
dise
ase o
r ot
her c
ause
s of c
ogni
tive i
mpa
irmen
t on
the c
ompu
ted
tom
ogra
phy
or m
agne
tic re
sona
nce i
mag
ing
McL
augh
lin et
al.
(192
) Qu
ébec
16M
= 7
6.2,
SD
= 5
.3F:
6
(37.
5%)
M: 1
0 (6
2.5%
)
Cauc
asian
: 14
(87.
5%);
Non-
Cauc
asian
: 2
(12.
5%)
M =
14.
9,
SD =
2.9
Peter
sen(2
7)M
= 2
7.4,
SD
= 1
.6HA
DS-
Depr
essio
n:
M =
2.8
, SD
= 2.
7
Obse
rv.
Exclu
sion:
Hist
ory
of st
roke
, TIA
, neu
rolo
gica
l or
psyc
hiatr
ic ill
ness
, hea
d in
jury
, sub
stanc
e abu
se,
eleva
ted sc
ores
on
the H
ADS,
unc
orre
cted
visu
al im
pairm
ent,
or si
gnifi
cant
hea
ring
impa
irmen
t
Pelts
ch et
al.(1
93)
Ontar
io22
M =
76,
SD
= 8
F: 1
2 (5
4.55
%)
M: 1
0 (4
5.45
%)
M =
14,
SD
= 4
Peter
sen(1
24)
M =
27,
SD
= 2
Obse
rv.
Exclu
sion:
Unc
orre
cted
visu
al im
pairm
ent,
visu
al or
ps
ychi
atric
sym
ptom
s oth
er th
an A
D an
d aM
CI
Peter
s et a
l.(194
) Qu
ébec
40M
=
72.5
3,
SD =
6.
84
F: 2
3 (5
7.5%
) M
: 17
(42.
5%)
M =
13.
36,
SD =
5.0
5Pe
terse
n(154
) M
=27
.70,
SD
= 1
.72
Obse
rv.
Exclu
sion:
Alco
holis
m, g
ener
al an
esth
esia
in th
e las
t 6
mon
ths,
pres
ence
or h
istor
y of
seve
re p
sych
iatric
di
sord
er, i
ntell
ectu
al di
sabi
lity,
neur
olog
ical d
iseas
e or
even
t (e.g
., str
oke,
PD, e
pilep
sy, b
rain
anox
ia),
psyc
hiatr
ic di
sord
er (e
.g.,
schi
zoph
reni
a, M
DD),
TBI,
or
syste
mic
dise
ase t
hat m
ay im
pair
cogn
ition
Wu
et al.
(195
) Qu
ébec
13M
= 6
9,
SD =
5.
69
F: 7
(5
3.85
%)
M: 6
(4
6.15
%)
M =
13.
15,
SD =
3.0
2Pe
terse
n(27)
M =
26.2
3,
SD =
2.0
5Ob
serv
.Ex
clusio
n: N
euro
logi
cal d
iseas
e (e.g
., str
oke,
PD, o
ther
ne
urod
egen
erati
ve d
iseas
es),
pres
ence
of a
ny m
ajor
struc
tura
l abn
orm
alitie
s or s
igns
of m
ajor v
ascu
lar
path
olog
y; A
xis 1
psy
chiat
ric d
isord
er o
r int
ellec
tual
disa
bilit
y, us
e of p
sych
oacti
ve su
bstan
ce, p
revi
ous o
r pr
esen
t use
of c
holin
ester
ase i
nhib
itor
Calla
han
et al.
(196
) Qu
ébec
35M
=
73.1
9,
SD =
7.
32
F: 1
6 (4
5.71
%)
M: 1
6 (4
5.71
%)
M =
12.
88,
SD =
5.11
Peter
sen(2
7)M
=23.
16,
SD =
2.55
GDS:
M =
9.
09, S
D =
3.05
Obse
rv.
Exclu
sion:
Hist
ory
of n
euro
logi
cal a
nd ce
rebr
ovas
cular
di
seas
e, pa
st or
curre
nt p
sych
iatric
illn
ess (
othe
r tha
n M
DD),
TBI,
histo
ry o
f alco
holis
m, u
ntre
ated
med
ical o
r m
etabo
lic co
nditi
ons,
gene
ral a
nesth
esia
or E
CT in
the
past
12 m
onth
s, pa
st in
tracr
anial
surg
ery,
unco
rrecte
d he
arin
g or
visu
al im
pairm
ent
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
318CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
Clou
tier e
t al.(1
97)
Québ
ec12
1M
=
70.5
4,
SD =
8.
21
F: 7
4 (6
1.16
%)
M: 4
7 (3
8.84
%)
M =
14.
46,
SD =
4.1
6Pe
terse
n(128
,147
)M
=27
.23,
SD
= 2
.22
GDS:
M =
15
.00,
SD
= 3.
66
Long
Exclu
sion:
Unc
orre
cted
visio
n or
hea
ring
impa
irmen
t, cu
rrent
ly o
n AD-
relat
ed m
edica
tion,
long
tim
e use
of
anxi
olyt
ics an
d an
tidep
ress
ant,
seve
re d
iagno
sis
of an
y se
vere
psy
chiat
ric d
isord
er, c
urre
nt m
ajor
med
ical c
ondi
tion,
curre
nt o
r pas
t alco
hol o
r sub
stanc
e ab
use,
signi
fican
t cer
ebro
vasc
ular
, neu
rolo
gica
l, or
ne
urod
egen
erati
ve d
isord
ers,
strok
e, or
larg
e-ve
ssel
dise
ase,
or g
ener
al an
esth
esia
with
in th
e las
t 6 m
onth
s
Gaud
reau
et
al.(1
98)
Québ
ec30
M =
73.
9,
SD =
6.1
F: 1
8 (6
0%) M
: 12
(40%
)
M =
13.
6,
SD =
5.3
NIA-
AA(1
8)M
= 2
3, S
D =
3.2
GDS:
M
= 6.
8, S
D =
4.6
Obse
rv.
Exclu
sion:
Hist
ory
of T
BI, s
troke
or o
ther
ce
rebr
ovas
cular
dise
ase,
delir
ium
(in
the p
ast 6
mon
ths),
fo
rmal
intra
cran
ial su
rger
y, ne
urol
ogica
l diso
rder
of
cere
bral
orig
inal
or an
othe
r dem
entia
state
, enc
epha
litis
or b
acter
ial m
enin
gitis
, uns
table
meta
bolic
or m
edica
l co
nditi
on, c
urre
nt o
r pas
t diag
nosis
of p
sych
iatric
ill
ness
or d
emen
tia ac
cord
ing
to D
SM-IV
, onc
olog
ical
treatm
ent i
n th
e pas
t 12
mon
ths,
subs
tance
addi
ction
ac
cord
ing
to th
e DSM
-IV, g
ener
al an
aesth
esia
in th
e las
t 6
mon
ths,
unco
rrecte
d vi
sion
or h
earin
g pr
oblem
, use
of
expe
rimen
tal m
edica
tion
Le P
age e
t al.(1
99)
Québ
ec10
M =
72.
9,
SD =
6.
42
F: 9
(90%
) M
: 1
(10%
)
Grun
dman
et
al.(2
00)
M =
27.
8,
SD =
1.9
9M
=24.
3, S
D =2
.06
Obse
rv.
Exclu
sion:
Hist
ory
or p
hysic
al sig
ns o
f ath
eros
clero
sis
or in
flam
mati
on
Sheld
on et
al.(4
0)
Ontar
io16
M =
75.
1,
SD =
5.7
F: 6
(3
7.5%
) M
: 10
(62.
5%)
M =
15,
SD
= 2.
9Pe
terse
n(27)
M =
28.
4,
SD =
1.2
HADS
-De
pres
sion:
M
= 3
.3, S
D =
2.6
Obse
rv.
No m
entio
n of
exclu
sion
crite
ria.
ten B
rinke
et
al.(2
01)
Briti
sh
Colu
mbi
a39
M =
75
.15,
SD
=
3.74
F: 3
9 (1
00%
) Gr
ade 9
-12
with
out
certi
ficate
=
5; H
igh
scho
ol
dipl
oma =
10
; Tra
de o
r pr
ofes
siona
l ce
rtific
ate o
r di
plom
a = 5
; Un
iver
sity
certi
ficate
or
dipl
oma =
8;
Univ
ersit
y de
gree
= 11
Peter
sen(1
22)
M =
27.1
5,
SD =
2.0
5M
=22.
09,
SD =
3.19
GDS:
M =
0.
77, S
D =
1.46
RCT
Exclu
sion:
Cur
rent
med
icatio
n fo
r whi
ch ex
ercis
e is
cont
rain
dica
ted, p
artic
ipate
d re
gular
ly in
resis
tance
tra
inin
g or
aero
bic t
rain
ing
in th
e las
t 6 m
onth
s, ne
urod
egen
erati
ve d
iseas
e/stro
ke, p
sych
iatric
diag
nosis
, de
men
tia o
f any
type
, ina
bilit
y to
spea
k or
und
ersta
nd
Engl
ish fl
uent
ly, E
RT
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
319CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
Bray
et et
al.(2
02)
Québ
ec32
M =
63
.96,
SD
=
6.97
F: 1
0 (3
1.25
%)
M: 2
2 (6
8.75
%)
M =
12.
53,
SD =
3.6
7NI
A-AA
(18)
M =
27.5
1,
SD =
2.1
3Ob
serv
.Ex
clusio
n: d
emen
tia ac
cord
ing
to D
SM-5
, slee
p ap
nea,
narc
olep
sy, e
xces
sive d
aytim
e slee
pine
ss, R
EM
sleep
beh
avio
ur d
isord
er, m
ajor p
sych
iatric
diso
rder
, su
bstan
ce ab
use,
histo
ry o
f stro
ke o
r bra
in in
jury
, un
cont
rolle
d hy
perte
nsio
n or
diab
etes,
COPD
, bra
in
tum
our,
ence
phali
tis, o
r EEG
abno
rmali
ties s
ugge
stive
of
epile
psy
Burh
an et
al.(2
03)
Ontar
io10
M =
72.
7,
SD =
9.3
F: 1
0 (1
00%
) M
= 1
0.5,
SD
= 0
.8Pe
terse
n(124
)M
= 2
2.2,
SD
= 2
.5GD
S-15
: M
= 2.
6, S
D =
2.7
Obse
rv.
Exclu
sion:
neu
rode
gene
rativ
e illn
ess (
any
form
of
dem
entia
or P
D) st
roke
, TBI
, epi
lepsy
, any
majo
r men
tal
illne
ss (e
.g.,
MDD
, bip
olar
diso
rder
, sch
izoph
reni
a, or
subs
tance
diso
rder
), cu
rrent
ly o
n an
y co
gniti
ve
enha
ncer
s
Calla
han
et al.
(204
) Qu
ébec
54M
=
74.4
4,
SD =
6.
07
F: 2
8 (5
1.85
%)
M: 2
6 (4
8.15
%)
M =
13.
49,
SD =
5.1
9Pe
terse
n(27)
M=2
3.37
, SD
=3.
42M
= 6
.67,
SD
=2.
59Ob
serv
.Ex
clusio
n: h
istor
y of
neu
rolo
gica
l dise
ase,
TBI,
strok
e, ps
ychi
atric
illne
ss (o
ther
than
dep
ress
ion)
, sub
stanc
e ab
use,
untre
ated
meta
bolic
cond
ition
, unc
orre
cted
visu
al/au
dito
ry im
pairm
ent,
intra
cran
ial su
rger
y, no
r gen
eral
anae
sthes
ia or
onc
olog
ical t
reatm
ent i
n th
e pas
t 6 m
onth
s
Davi
dson
et al
.(41)
Ontar
io19
M =
75
.63,
SD
=
6.23
F: 1
0 (5
2.63
%)
M: 9
(4
7.37
%)
M =
16.
68,
SD =
3.9
6Pe
terse
n(122
) M
=22.
79,
SD =
3.09
Obse
rv.
No m
entio
n of
exclu
sion
crite
ria. E
xclu
ded
one
parti
cipan
t with
poo
r hea
ring,
one
with
ver
y lo
w M
oCA
scor
e (11
/30)
, and
thre
e ind
ivid
uals
who
deve
lope
d de
men
tia (2
with
Alzh
eimer
’s di
seas
e and
1 fr
onto
-tem
pora
l dem
entia
) fro
m d
ata an
alyse
s
Lang
lois
et al.
(205
) Qu
ébec
20M
= 7
7,
SD =
6.5
F: 1
4 (7
0%) M
: 6
(30%
)
M =
15,
SD
= 4.
4NI
A-AA
(18)
M =
26,
SD
= 2.
4Ob
serv
.Ex
clusio
n: H
istor
y of
syste
mic
or n
euro
logi
cal d
iseas
e, TB
I, ps
ychi
atric
illne
ss, h
istor
y of
alco
hol o
r dru
g ab
use,
untre
ated
med
ical o
r meta
bolic
cond
ition
, gen
eral
anes
thes
ia in
the p
ast 6
mon
ths
Nasre
ddin
e &
Patel
(206
) Qu
ébec
25M
=
72.6
9Pe
terse
n(27)
M=2
1.24
, SD
=3.
57Ob
serv
.Ex
clusio
n: H
istor
y of
cent
ral n
ervo
us sy
stem
diso
rder
, or
any
cond
ition
that
may
acco
unt f
or co
gniti
ve d
eficit
, no
lear
ning
disa
bilit
y, att
entio
n de
ficit
diso
rder
, or
men
tal re
tarda
tion,
no
phys
ical d
isabi
lity
that
woul
d in
fluen
ce te
st re
sults
, not
pre
-exi
sting
or c
urre
nt
psyc
hiatr
ic ill
ness
es (e
xcep
t for
thos
e who
with
pre
viou
s de
pres
sion
with
out h
ospi
taliza
tion
and
has a
GDS
scor
e of
less
than
6 in
the l
ast 6
mon
ths),
on
any
unsta
ble d
ose
of m
edica
tion
that
affe
cts th
e cen
tral n
ervo
us sy
stem
, cu
rrent
ly o
n an
tiepi
leptic
med
icatio
n, n
euro
leptic
s, m
ust
not h
ave a
scor
e gre
ater t
han
7 on
the s
ubjec
tive m
emor
y sc
ale, a
lcoho
l con
sum
ptio
n ex
ceed
ing
the p
erm
itted
lim
it (3
or m
ore 2
00 m
l drin
ks o
f 5 to
7%
alco
hol p
er d
ay fo
r m
en; a
nd 2
or m
ore 2
00m
l drin
ks o
f 5 to
7%
of a
lcoho
l pe
r day
for w
omen
, and
1 o
r mor
e 200
ml d
rink
of 3
5%
alcoh
ol p
er d
ay fo
r men
and
wom
en, c
onsu
med
dru
gs in
th
e pas
t 5 y
ears.
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
320CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
Teas
dale
et al.
(30)
Québ
ec15
M =
71.
1,
SD =
9F:
2
(13.
33%
) M
: 13
(86.
67%
)
M =
14.3
, SD
= 2.
5NI
A-AA
(18)
M =
24.
3,
SD =
2.5
GDS:
M
= 4.
8, S
D =
3.8
Obse
rv.
No m
entio
n of
exclu
sion
crite
ria
Valle
t et a
l.(207
) Qu
ébec
16M
=
78.1
9,
SD =
6.1
F: 11
(6
8.75
%)
M: 5
(3
1.25
%)
M =
14.
94,
SD =
4.1
0Pe
terse
n (1
8,23
)M
=28
.31,
SD
= 1
.5M
=25.
62,
SD =
2.1
Obse
rv.
Exclu
sion:
Med
ical h
istor
y of
or c
urre
ntly
taki
ng
med
icatio
ns fo
r con
ditio
ns w
ith k
nown
sens
ory
or
neur
olog
ical e
ffects
; par
ticip
ants
with
diag
nose
s of
depr
essio
n an
d/or
anxi
ety w
ere i
nclu
ded
if th
ey w
ere
stabl
e on
med
icatio
n or
non
-sym
ptom
atic a
t the
tim
e of
stud
y
Bocti
et al
.(208
) Qu
ébec
42M
=
69.6
2,
SD =
9.
31
F: 2
0 (4
7.62
%)
M: 2
2 (5
2.38
%)
M =
12.
27,
SD =
5.0
7Ch
ertk
ow et
al.
(130
) M
=27
.93,
SD
= 1
.83
M=2
3.22
, SD
=3.
86Cr
oss-s
ect
Exclu
sion:
seve
re p
sych
iatric
or s
ystem
ic di
sord
er,
cogn
itive
impa
irmen
t attr
ibut
ed to
larg
e ves
sel s
troke
, TB
I, alc
ohol
abus
e, sle
ep ap
nea,
or ca
ncer
and
relat
ed
treatm
ent
Calla
han
et al.
(209
) Qu
ébec
58M
=
73.9
3,
SD =
6.
67
F: 2
9 (5
0%) M
: 29
(50%
)
M =
13.
54,
SD =
3.9
8Pe
terse
n(27)
M=2
3.69
, SD
=3.
03GD
S: M
=
6.85
, SD
= 2.
19
Obse
rv.
Exclu
sion:
Hist
ory
of n
euro
logi
cal d
iseas
e, br
ain in
jury
, str
oke,
psyc
hiatr
ic ill
ness
(oth
er th
an d
epre
ssio
n),
subs
tance
abus
e, ge
nera
l ane
sthes
ia, in
tracr
anial
surg
ery
or o
ncol
ogic
treatm
ent i
n th
e pas
t 6 m
onth
s, or
unt
reate
d m
etabo
lic co
nditi
ons,
or u
ncor
recte
d vi
sual/
audi
tory
im
pairm
ent
Croc
kett
et al.
(210
) Br
itish
Co
lum
bia
40M
=
76.7
5,
SD =
5.8
F: 2
1 (5
2.5%
) M
: 19
(47.
5%)
Peter
sen(1
22)
M =
27.
5,
SD =
1.3
M =
22.
3,
SD =
2.7
Cros
s-sec
tEx
clusio
n: F
orm
al di
agno
sis o
f neu
rode
gene
rativ
e di
seas
e, str
oke,
dem
entia
of a
ny ty
pe, o
r psy
chiat
ric
cond
ition
s, cli
nica
lly si
gnifi
cant
neu
ropa
thy
or
seve
re m
uscu
losk
eletal
or j
oint
dise
ase,
curre
ntly
on
psyc
hotro
pic m
edica
tion,
hav
e a h
istor
y of
caro
tid
sinus
sens
itivi
ty, li
ving
in a
nursi
ng h
ome,
exten
ded
care
facil
ity, o
r ass
isted
-car
e fac
ility,
ineli
gibl
e for
MRI
sc
anni
ng
Hird
et al
.(31)
Ontar
io24
M =
66.
5,
SD =
9.5
F: 1
0 (4
1.67
%)
M: 1
4 (5
8.33
%)
M =
15,
SD
= 2.
6NI
A-AA
(18)
M =
23.
8,
SD =
1.9
Obse
rv.
No m
entio
n of
exclu
sion
crite
ria
Knez
evic
et al.
(211
) On
tario
11M
=
71.9
1,
SD =
5.3
F: 6
(5
4.55
%)
M: 5
(4
5.45
%)
M =
15.
82,
SD =
2.3
6Pe
terse
n(27)
M =
27.
3,
SD =
1.9
5M
= 2
1.7,
SD
= 3
.6Ob
serv
.Ex
clusio
n: C
oncu
rrent
Axi
s I D
SM-IV
diso
rder
, hist
ory
of cl
osed
hea
d in
jury
with
loss
of c
onsc
ious
ness
, stro
ke,
or o
ther
neu
rolo
gica
l diso
rder
with
cent
ral n
ervo
us
syste
m in
volv
emen
t
Le P
age e
t al.(2
12)
Québ
ec13
M =
72.
8,
SD =
3.
64
F: 9
(6
9.23
%)
M: 4
(3
0.77
%)
Grun
dman
et
al.(2
00)
M =
26.7
5,
SD =
1.5
M =
24, S
D =2
.95
Obse
rv.
Exclu
sion:
Hist
ory
or p
hysic
al sig
ns o
f ath
eros
clero
sis
or in
flam
mati
on
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
321CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
Mah
et al
.(213
) On
tario
16M
= 7
3.5,
SD
= 7
F: 1
3 (8
1.25
%)
M: 3
(1
8.75
%)
Cauc
asian
: 16
(100
%)
M =
15.
6,
SD =
3.5
Peter
sen(1
24)
M =
27.
8,
SD =
1.6
GDS:
M
= 2.
1, S
D =
2.8
Obse
rv.
Exclu
sion:
Inab
ility
to sp
eak/
unde
rstan
d En
glish
, M
MSE
scor
e < 2
6, h
istor
y of
neu
rolo
gica
l diso
rder
, un
stabl
e med
ical c
ondi
tions
, cur
rent
ly ta
king
ps
ycho
tropi
c med
icatio
n
Mon
tero-
Odas
so
et al.
(214
) On
tario
112
M =
75
.97,
SD
=
6.88
F: 5
5 (4
9.11
%)
M: 5
7 (5
0.89
%)
Peter
sen(1
28,1
47)
M =
27.4
6,
SD =
2.4
6M
=23.
14,
SD =
3.39
Pros
pect
coho
rtEx
clusio
n: In
abili
ty to
spea
k/un
derst
and
Engl
ish, a
ny
neur
olog
ical c
ondi
tion/
dise
ase w
ith m
otor
defi
cits,
mus
culo
skele
tal d
isord
er o
f low
er li
mbs
affe
cting
gait
pe
rform
ance
, use
of n
euro
leptic
s or b
enzo
diaz
epin
es,
MDD
O’Ca
oim
h et
al.(2
15)
Ontar
io76
6M
=
75.3
0,
SD =
7.
43
F: 4
03
(52.
61%
) M
: 363
(4
7.39
%)
M =
12,
SD
= 2.
97Pe
terse
n(122
)SM
MSE
: M
=27.
65, S
D =
2.23
Obse
rv.
Exclu
sion:
Miss
ing
dem
ogra
phic
info
rmati
on, a
ny
dem
entia
, acti
ve d
epre
ssio
n, o
r unc
lear d
iagno
sis;
indi
vidu
als w
ith m
issin
g da
ta in
key
mea
sure
s wer
e also
ex
clude
d
Belle
ville
et
al.(2
16)
Québ
ec12
7M
=
72.1
9,
SD =
7.
28
F: 7
0 (5
5.12
%)
M: 5
7 (4
4.88
%)
M =
14.
67,
SD =
3.8
5Pe
terse
n(128
)M
=24.
44,
SD =
3.02
GDS:
M =
3.
27, S
D =
3.05
Sing
le bl
ind
RCT
Exclu
sion:
Cur
rent
psy
chiat
ric, c
ereb
rova
scul
ar
or n
euro
logi
cal d
isord
er, s
ubsta
nce a
buse
, gen
eral
anes
thes
ia in
the p
ast 6
mon
ths,
signi
fican
t phy
sical
mob
ility
impa
irmen
t, pr
obab
le or
pos
sible
dem
entia
, M
MSE
< 2
4, co
gniti
ve im
pairm
ent s
igni
fican
tly
impa
cting
func
tiona
l ind
epen
denc
e
Crot
eau
et al.
(217
)Qu
ébec
20M
= 7
6.9,
SD
= 5
.8F:
11
(55%
) M:
9 (4
5%)
Peter
sen(2
7)M
= 2
7.5,
SD
= 2
Obse
rv.
Exclu
sion:
smok
ing,
subs
tance
abus
e, un
treate
d or
un
cont
rolle
d hy
perte
nsio
n, d
yslip
idem
ia, d
iabete
s
Dunc
an et
al.(4
5)
Québ
ec68
M =
73
.65,
SD
=
1.00
F: 3
2 (4
7.06
%)
M: 3
6 (5
2.94
%)
M =
12.
4,
SD =
0.7
1Ga
uthi
er et
al.(1
69)
adap
ted fr
om
Peter
sen(1
28)
M=2
7.15
, SD
=0.
36Ob
serv
.Ex
clusio
n: L
eft-h
ande
dnes
s, co
gniti
ve fu
nctio
n re
verti
ng to
“nor
mal”
after
initi
al M
CI d
iagno
sis
Good
man
et
al.(2
18)
Ontar
io34
M =
74.
8,
SD =
5.9
F:
18
(52.
94%
) M
: 16
(47.
06%
)
Cauc
asian
: 23
(68%
); No
n-Ca
ucas
ian: 1
1 (3
2%)
M =
15.
2,
SD =
2.3
DSM
-5(2
19)
M =
27.
6,
SD =
3.1
Obse
rv.
Exclu
sion:
Age
<60
yea
rs, M
ADRS
≥ 1
0, D
SM-5
cr
iteria
for M
DD in
the p
ast 1
0 ye
ars,
lifeti
me d
iagno
sis
of sc
hizo
phre
nia,
bipo
lar d
isord
er, o
r OCD
, diag
nosis
of
alcoh
ol o
r oth
er su
bstan
ce u
se d
isord
er w
ithin
the l
ast
12 m
onth
s, sig
nific
ant n
euro
logi
cal c
ondi
tion,
use
of
cogn
itive
enha
ncer
med
icatio
n wi
thin
the p
ast 6
wee
ks,
MoC
A <
26, M
MSE
< 2
4
Hsu
et al.
(220
) BC
49M
= 7
5.4,
SD
= 6
.3
F: 3
0 (6
1.22
%)
M: 1
9 (3
8.78
%)
NIA-
AA(1
8)M
= 2
7.6,
SD
= 1
.4M
= 2
2.3,
SD
= 2
.6Cr
oss-s
ect
Exclu
sion:
For
mal
diag
nosis
of n
euro
dege
nera
tive
dise
ase,
strok
e, an
y de
men
tia, p
sych
iatric
cond
ition
, cli
nica
lly si
gnifi
cant
neu
ropa
thy
or se
vere
m
uscu
losk
eletal
or j
oint
dise
ase,
takin
g ps
ycho
tropi
c m
edica
tion
or m
edica
tions
that
may
affe
ct co
gniti
on,
not e
xpec
ted to
star
t or a
re st
able
on fi
xed
dose
of
antid
emen
tia m
edica
tion
in th
e 12-
mon
th st
udy
perio
d,
a hist
ory
of ca
rotid
sinu
s sen
sitiv
ity, l
ivin
g in
a nu
rsing
ho
me,
exten
ded
care
facil
ity, o
r ass
isted
-car
e fac
ility,
in
eligi
ble f
or M
RI sc
anni
ng
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
322CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
App
endi
x B
. Con
tinue
d
Art
icle
Pr
ovin
ceSa
mpl
e Si
zeA
geSe
x R
ace/
E
thni
city
Edu
catio
nD
iagn
ostic
C
rite
ria
MM
SEM
oCA
Dep
ress
ion
Mea
sure
(s)
Stud
y D
esig
nIn
clus
ion/
Exc
lusi
on C
rite
ria
MCI
-PD
Artic
les
Matt
eau
et al.
(172
) Qu
ébec
22M
= 6
8.3,
SD
= 9
.3F:
10
(45.
45%
) M
: 12
(54.
55%
)
M =
13.
1,
SD =
4.5
Peter
sen
(27,
147)
M =
27.
8,
SD =
1.4
HAM
D: M
=
4.0,
SD
= 3.
1
Obse
rv.
Exclu
sion:
Acu
te ep
isode
of M
DD d
eterm
ined
by
HAM
D (sc
ores
> 1
3), a
ny n
euro
logi
cal o
r sys
temic
prob
lems o
ther
than
PD
and A
D kn
own
to af
fect
cogn
ition
(e.g
., TB
I, tu
mou
r), d
eep
brain
stim
ulati
on o
r ot
her b
rain
neu
rosu
rger
y, cu
rrent
or p
ast a
lcoho
l or d
rug
abus
e, ch
roni
c psy
chiat
ric il
lnes
s
Ville
neuv
e et
al,(2
21)
Québ
ec18
M =
67
.72,
SD
=
7.71
M =
15.
06,
SD =
3.9
9Pe
terse
n(154
)M
=28
.39,
SD
= 0
.98
Obse
rv.
Exclu
sion:
Dem
entia
or M
DD ac
cord
ing
to D
SM-IV
-TR
, slee
p ap
nea i
ndex
> 2
0, ab
norm
al EE
G su
gges
tive
of ep
ileps
y, un
stabl
e diab
etes o
r hyp
erten
sion,
en
ceph
alitis
, age
> 9
0, la
ngua
ge o
ther
than
Fre
nch
or
Engl
ish, p
rimar
y sc
hool
unc
ompl
eted
Hang
anu
et al.
(32)
Québ
ec18
M =
64.
7,
SD =
4.5
F: 5
(2
7.78
%)
M: 1
3 (7
2.22
%)
M =
13.
4,
SD =
3.2
The M
ovem
ent
Diso
rder
Soc
iety
Task
For
ce(2
22)
M =
26.
5,
SD =
1.6
Obse
rv.
No m
entio
n of
exclu
sion
crite
ria
Chris
toph
er et
al.
(223
) On
tario
11M
= 7
0.8,
SD
=
7.01
F: 3
(2
7.27
%)
M: 8
(7
2.73
%)
M =
16.
2,
SD =
1.4
7Th
e Mov
emen
t Di
sord
er S
ociet
y Ta
sk F
orce
(222
)
M =
23.
2,
SD =
2.79
BDI-I
I: M
=
5.54
, SD
= 5.
87
Obse
rv.
Exclu
sion:
any
othe
r neu
rolo
gica
l or p
sych
iatric
co
nditi
on, d
emen
tia
Hang
anu
et al.
(224
) Qu
ébec
17M
=
64.0
1,
SD =
5.
36
F: 6
(3
5.29
%);
M: 1
1 (6
4.71
%)
M =
13.
47,
SD =
3.3
7Th
e Mov
emen
t Di
sord
er S
ociet
y Ta
sk F
orce
(222
)
M=2
6.25
, SD
=2.
02Ob
serv
.Ex
clusio
n: E
vide
nce o
f cog
nitiv
e abn
orm
alitie
s not
att
ribut
ed to
age.
Naga
no-S
aito
et al.
(33)
Qu
ébec
14M
= 6
3.7,
SD
=
5.01
F: 5
(3
5.71
%)
M: 9
(6
4.29
%)
M =
12.
9,
SD =
2.4
6Th
e Mov
emen
t Di
sord
er S
ociet
y Ta
sk F
orce
(222
)
M =
26.
5,
SD =
1.79
BDI-I
I: M
=
11.1
, SD
= 6.
57
Obse
rv.
No m
entio
n of
exclu
sion
crite
ria
MCI
-VD
Artic
le
Gu et
al.(4
4)
Ontar
io20
M =
66
.15
M =
14.
45NI
A-AA
(18)
alon
g wi
th
imag
ing
data
M =
27.
56Ob
serv
.Ex
clusio
n: R
ever
sible
caus
es o
f dem
entia
(TSH
, B12
, fo
late d
eficie
ncy)
Stud
y D
esig
ns: R
CT
= ra
ndom
ized
con
trol t
rial;
Obs
erv.
= o
bser
vatio
nal;
Pros
pect
coh
ort =
pro
spec
tive
coho
rt; N
-ran
d fe
asib
il =
non-
rand
omiz
ed fe
asib
ility
; Cro
ss-s
ect =
cro
ss-s
ectio
nal;
Pros
pect
long
=
pros
pect
ive
long
itudi
nal;
Cro
ss-s
ect d
ata
extra
c lo
ng =
Cro
ss-s
ectio
nal d
ata
extra
cted
from
a lo
ngitu
dina
l stu
dy.
AD
= A
lzhe
imer
’s d
isea
se; B
12 =
Vita
min
B12
; BD
I-II
= B
eck
Dep
ress
ion
Inve
ntor
y-II
; CO
PD =
chr
onic
obs
truct
ive
pulm
onar
y di
seas
e; C
T =
com
pute
d to
mog
raph
y; C
VD
= c
ardi
ovas
cula
r dis
ease
; DSM
-IV
-TR
= D
iagn
ostic
and
Sta
tistic
al M
anua
l of M
enta
l Dis
orde
r, fo
urth
edi
tion,
text
revi
sion
; EC
T =
elec
troco
nvul
sive
ther
apy;
EEG
= e
lect
roen
ceph
alog
raph
y; E
RT =
est
roge
n re
plac
emen
t the
rapy
; GD
S =
Ger
iatri
c D
epre
ssio
n Sc
ale;
HA
DS
= H
ospi
tal A
nxie
ty a
nd D
epre
ssio
n Sc
ale;
HA
MD
= H
amilt
on D
epre
ssio
n R
atin
g Sc
ale;
ICD
= In
tern
atio
nal C
lass
ifica
tion
of D
isea
ses;
MA
DR
S =
Mon
tgom
ery–
Åsb
erg
Dep
ress
ion
Rat
ing
Scal
e; M
DD
= m
ajor
dep
ress
ive
diso
rder
; MR
I = m
agne
tic re
sona
nce
imag
ing;
NIA
-AA
= N
atio
nal I
nstit
ute
on A
ging
and
Alz
heim
er’s
Ass
ocia
tion;
OC
D =
obs
essi
ve c
ompu
lsiv
e di
sord
er;
PD =
Par
kins
on’s
dis
ease
; REM
= e
ye m
ovem
ent;
SMM
SE =
Sta
ndar
dize
d M
ini-M
enta
l Sta
tus E
xam
; TB
I = tr
aum
atic
bra
in in
jury
; TIA
= tr
ansi
ent i
sche
mic
atta
ck; T
SH =
thyr
oid
stim
ulat
ing
horm
one.
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
323CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
MCI
-PD
Artic
les
Matt
eau
et al.
(172
) Qu
ébec
22M
= 6
8.3,
SD
= 9
.3F:
10
(45.
45%
) M
: 12
(54.
55%
)
M =
13.
1,
SD =
4.5
Peter
sen
(27,
147)
M =
27.
8,
SD =
1.4
HAM
D: M
=
4.0,
SD
= 3.
1
Obse
rv.
Exclu
sion:
Acu
te ep
isode
of M
DD d
eterm
ined
by
HAM
D (sc
ores
> 1
3), a
ny n
euro
logi
cal o
r sys
temic
prob
lems o
ther
than
PD
and A
D kn
own
to af
fect
cogn
ition
(e.g
., TB
I, tu
mou
r), d
eep
brain
stim
ulati
on o
r ot
her b
rain
neu
rosu
rger
y, cu
rrent
or p
ast a
lcoho
l or d
rug
abus
e, ch
roni
c psy
chiat
ric il
lnes
s
Ville
neuv
e et
al,(2
21)
Québ
ec18
M =
67
.72,
SD
=
7.71
M =
15.
06,
SD =
3.9
9Pe
terse
n(154
)M
=28
.39,
SD
= 0
.98
Obse
rv.
Exclu
sion:
Dem
entia
or M
DD ac
cord
ing
to D
SM-IV
-TR
, slee
p ap
nea i
ndex
> 2
0, ab
norm
al EE
G su
gges
tive
of ep
ileps
y, un
stabl
e diab
etes o
r hyp
erten
sion,
en
ceph
alitis
, age
> 9
0, la
ngua
ge o
ther
than
Fre
nch
or
Engl
ish, p
rimar
y sc
hool
unc
ompl
eted
Hang
anu
et al.
(32)
Québ
ec18
M =
64.
7,
SD =
4.5
F: 5
(2
7.78
%)
M: 1
3 (7
2.22
%)
M =
13.
4,
SD =
3.2
The M
ovem
ent
Diso
rder
Soc
iety
Task
For
ce(2
22)
M =
26.
5,
SD =
1.6
Obse
rv.
No m
entio
n of
exclu
sion
crite
ria
Chris
toph
er et
al.
(223
) On
tario
11M
= 7
0.8,
SD
=
7.01
F: 3
(2
7.27
%)
M: 8
(7
2.73
%)
M =
16.
2,
SD =
1.4
7Th
e Mov
emen
t Di
sord
er S
ociet
y Ta
sk F
orce
(222
)
M =
23.
2,
SD =
2.79
BDI-I
I: M
=
5.54
, SD
= 5.
87
Obse
rv.
Exclu
sion:
any
othe
r neu
rolo
gica
l or p
sych
iatric
co
nditi
on, d
emen
tia
Hang
anu
et al.
(224
) Qu
ébec
17M
=
64.0
1,
SD =
5.
36
F: 6
(3
5.29
%);
M: 1
1 (6
4.71
%)
M =
13.
47,
SD =
3.3
7Th
e Mov
emen
t Di
sord
er S
ociet
y Ta
sk F
orce
(222
)
M=2
6.25
, SD
=2.
02Ob
serv
.Ex
clusio
n: E
vide
nce o
f cog
nitiv
e abn
orm
alitie
s not
att
ribut
ed to
age.
Naga
no-S
aito
et al.
(33)
Qu
ébec
14M
= 6
3.7,
SD
=
5.01
F: 5
(3
5.71
%)
M: 9
(6
4.29
%)
M =
12.
9,
SD =
2.4
6Th
e Mov
emen
t Di
sord
er S
ociet
y Ta
sk F
orce
(222
)
M =
26.
5,
SD =
1.79
BDI-I
I: M
=
11.1
, SD
= 6.
57
Obse
rv.
No m
entio
n of
exclu
sion
crite
ria
MCI
-VD
Artic
le
Gu et
al.(4
4)
Ontar
io20
M =
66
.15
M =
14.
45NI
A-AA
(18)
alon
g wi
th
imag
ing
data
M =
27.
56Ob
serv
.Ex
clusio
n: R
ever
sible
caus
es o
f dem
entia
(TSH
, B12
, fo
late d
eficie
ncy)
Stud
y D
esig
ns: R
CT
= ra
ndom
ized
con
trol t
rial;
Obs
erv.
= o
bser
vatio
nal;
Pros
pect
coh
ort =
pro
spec
tive
coho
rt; N
-ran
d fe
asib
il =
non-
rand
omiz
ed fe
asib
ility
; Cro
ss-s
ect =
cro
ss-s
ectio
nal;
Pros
pect
long
=
pros
pect
ive
long
itudi
nal;
Cro
ss-s
ect d
ata
extra
c lo
ng =
Cro
ss-s
ectio
nal d
ata
extra
cted
from
a lo
ngitu
dina
l stu
dy.
AD
= A
lzhe
imer
’s d
isea
se; B
12 =
Vita
min
B12
; BD
I-II
= B
eck
Dep
ress
ion
Inve
ntor
y-II
; CO
PD =
chr
onic
obs
truct
ive
pulm
onar
y di
seas
e; C
T =
com
pute
d to
mog
raph
y; C
VD
= c
ardi
ovas
cula
r dis
ease
; DSM
-IV
-TR
= D
iagn
ostic
and
Sta
tistic
al M
anua
l of M
enta
l Dis
orde
r, fo
urth
edi
tion,
text
revi
sion
; EC
T =
elec
troco
nvul
sive
ther
apy;
EEG
= e
lect
roen
ceph
alog
raph
y; E
RT =
est
roge
n re
plac
emen
t the
rapy
; GD
S =
Ger
iatri
c D
epre
ssio
n Sc
ale;
HA
DS
= H
ospi
tal A
nxie
ty a
nd D
epre
ssio
n Sc
ale;
HA
MD
= H
amilt
on D
epre
ssio
n R
atin
g Sc
ale;
ICD
= In
tern
atio
nal C
lass
ifica
tion
of D
isea
ses;
MA
DR
S =
Mon
tgom
ery–
Åsb
erg
Dep
ress
ion
Rat
ing
Scal
e; M
DD
= m
ajor
dep
ress
ive
diso
rder
; MR
I = m
agne
tic re
sona
nce
imag
ing;
NIA
-AA
= N
atio
nal I
nstit
ute
on A
ging
and
Alz
heim
er’s
Ass
ocia
tion;
OC
D =
obs
essi
ve c
ompu
lsiv
e di
sord
er;
PD =
Par
kins
on’s
dis
ease
; REM
= e
ye m
ovem
ent;
SMM
SE =
Sta
ndar
dize
d M
ini-M
enta
l Sta
tus E
xam
; TB
I = tr
aum
atic
bra
in in
jury
; TIA
= tr
ansi
ent i
sche
mic
atta
ck; T
SH =
thyr
oid
stim
ulat
ing
horm
one.
REFERENCES
* Articll diagnostic criteria used in articles included in the systematic review.
1. Petersen RC. Mild cognitive impairment. Continuum. 2016;22(2, De-mentia):404–18.
2. Stephan BCM, Brayne C, Savva GM, et al. Occurrence of medical co-morbidity in mild cognitive impairment: implications for generalisation of MCI research. Age Ageing. 2011;40(4):501–07.
3. Jongsma KR, van Bruchem-Visser RL, van de Vathorst S, et al. Has demen-tia research lost its sense of reality? A descriptive analysis of eligibility cri-teria of Dutch dementia research protocols. Neth J Med. 2016;74(5):201–09.
4. Trivedi RB, Humphreys K. Participant exclusion criteria in treatment research on neurological disorders: are unrepresentative study samples problematic? Contemp Clin Trials [Internet]. 2015;44:20–25. Available from: https://www.sciencedirect.com/science/article/pii/S155171441530046X
5. Zulman DM, Sussman JB, Chen X, et al. Examining the evidence: a sys-tematic review of the inclusion and analysis of older adults in randomized controlled trials. J Gen Intern Med. 2011;26(7):783–90.
6. Surman CBH, Monuteaux MC, Petty CR, et al. Representativeness of participants in a clinical trial for attention-deficit/hyperactivity disorder? Comparison with adults from a large observational study. J Clin Psychiatry. 2010;71(12):1612–16.
7. Statistics Canada. Public Health Agency. How healthy are Canadians? [Internet]. Ottawa, ON: Statistics Canada; 2017. Available from: https://www.canada.ca/en/public-health/services/publications/healthy-living/how-healthy-canadians.html
8. Statistics Canada. Health at a Glance. Mental and substance use disorders in Canada [archived]. Catalogue #82-624-X. Ottawa, ON: Statistics Can-ada; 2015.
9. Lopez OL, Jagust WJ, Dullberg C, et al. Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study. Arch Neurol. 2003;60(10):1394–99.
10. Liao W, Hamel REG, Olde Rikkert MGM, et al. A profile of The Clinical Course of Cognition and Comorbidity in Mild Cognitive Impairment and Dementia Study (The 4C study): two complementary longitudinal, clinical cohorts in the Netherlands. BMC Neurol [Internet]. 2016;16(1):242. Available from: https://link.springer.com/article/10.1186/s12883-016-0750-9
11. Plassman BL, Williams JW, Burke JR, Holsinger T, Benjamin S. Sys-tematic review: Factors associated with risk for and possible prevention of cognitive decline in later life. Ann Intern Med. 2010 Aug;153(3):182–93.
12. Tse E, Hogan D, Fischer K, et al. PROMPT: A prospective registry of persons with memory symptoms. In: Campus Alberta Neuroscience 2016 International Conference Abstracts. 2016. Abstract #86.
13. Hogan DB, Thierer DE, Ebly EM, et al. Progression and outcome of patients in a Canadian dementia clinic. Can J Neurol Sci. 1994;21(04):331–38.
14. Hu C, Yu D, Sun X, et al. The prevalence and progression of mild cognitive impairment among clinic and community populations: a systematic review and meta-analysis. Int Psychogeriatrics. 2017;29(10):1595–608.
15. Sheikh F, Ismail Z, Mortby ME, et al. Prevalence of mild behav-ioral impairment in mild cognitive impairment and subjective cognitive decline, and its association with caregiver burden. Int Psychogeriatrics. 2018;30(02):233–44.
16. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.
17. Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53(4):695–99.
18. Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cogni-tive impairment due to Alzheimer’s disease: recommendations from the Na-tional Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement. 2011;7(3):270–79.
19. De Mendonça A, Ribeiroa F, Guerreiro M, et al. Frontotemporal mild cognitive impairment. J Alzheimer’s Dis. 2004;6(1):1–9.
20. Donaghy PC, O’Brien JT, Thomas AJ. Prodromal dementia with Lewy bodies. Psychol Med. 2015;45(2):259–68.
21. Day GS, Lim TS, Hassenstab J, et al. Differentiating cognitive impair-ment due to corticobasal degeneration and Alzheimer disease. Neurology. 2017;88(13):1273–81.
22. Pilotto A, Gazzina S, Benussi A, et al. Mild cognitive impairment and progression to dementia in progressive supranuclear palsy. Neurodegener Dis. 2017;17(6):286–91.
23. Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cog-nitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(9):2672–713.
24. Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression screening scale—a preliminary report. J Psychiatr Res. 1983;17(1):37–49.
25. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1–e34.
26. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. Ann Intern Med. 2009;151(4):264–69.
27. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183–94.
*28. Kabani NJ, Sled JG, Chertkow H. Magnetization transfer ratio in mild cognitive impairment and dementia of Alzheimer’s type. Neuroimage. 2002;15(3):604–10.
*29. Phillips NA, Chertkow H, Leblanc MM, et al. Functional and anatomi-cal memory indices in patients with or at risk for Alzheimer’s disease. J Int Neuropsychol Soc. 2004;10(2):200–10.
*30. Teasdale N, Simoneau M, Hudon L, et al. Older adults with mild cogni-tive impairments show less driving errors after a multiple sessions simulator training program but do not exhibit long term retention. Front Hum Neurosci [Internet]. 2016;10(article 653):1–12. Available from: http://journal.frontier-sin.org/article/10.3389/fnhum.2016.00653/full
*31. Hird MA, Vesely KA, Fischer CE, et al. Investigating simulated driving errors in amnestic single- and multiple-domain mild cognitive impairment. J Alzheimer’s Dis. 2017;56(2):447–52.
*32. Hanganu A, Bedetti C, Jubault T, et al. Mild cognitive impairment in patients with Parkinson’s disease is associated with increased cortical degeneration. Movement Disord. 2013;28(10):1360–69.
*33. Nagano-Saito A, Habak C, Mejía-Constaín B, et al. Effect of mild cognitive impairment on the patterns of neural activity in early Parkinson’s disease. Neurobiol Aging [Internet]. 2014;35(1):223–31. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0197458013002868
*34. Levinoff EJ, Phillips NA, Verret L, et al. Cognitive estimation impair-ment in Alzheimer disease and mild cognitive impairment. Neuropsychology. 2006;20(1):123–32.
*35. Singh V, Chertkow H, Lerch JP, et al. Spatial patterns of cortical thinning in mild cognitive impairment and Alzheimer’s disease. Brain. 2006;129(11):2885–93.
*36. Houde M, Bergman H, Whitehead V, et al. A predictive depression pattern in mild cognitive impairment. Int J Geriatr Psychiatry. 2008;23(10):1028–33.
*37. Taler V, Klepousniotou E, Phillips NA. Comprehension of lexical am-biguity in healthy aging, mild cognitive impairment, and mild Alzheimer’s disease. Neuropsychologia. 2009;47(5):1332–43.
*38. Barnabe A, Whitehead V, Pilon R, et al. Autobiographical memory in mild cognitive impairment and Alzheimer’s disease: a comparison be-tween the Levine and Kopelman interview methodologies. Hippocampus. 2012;22(9):1809–25.
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
324CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
*39. Brambati SM, Peters F, Belleville S, et al. Lack of semantic priming effects in famous person recognition in Mild Cognitive Impairment. Cortex. 2012;48(4):414–20.
*40. Sheldon S, Vandermorris S, Al-Haj M, et al. Ill-defined problem solving in amnestic mild cognitive impairment: linking episodic memory to effective solution generation. Neuropsychologia. 2015;68:168–75.
*41. Davidson PSR, Cooper L, Taler V. Remembering a visit to the psych-ology lab: implications of mild cognitive impairment. Neuropsychologia [Internet]. 2016;90:243–50. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0028393216302731
*42. Standish TI, Molloy DW, Cunje A, et al. Do the ABCS 135 short cognitive screen and its subtests discriminate between normal cogni-tion, mild cognitive impairment and dementia? Int J Geriatr Psychiatry. 2007;22(3):189–94.
*43. Xie H, Mayo N, Koski L. Predictors of future cognitive decline in persons with mild cognitive impairment. Dement Geriatr Cogn Disord. 2011;32(5):308–17.
*44. Gu J, Fischer CE, Saposnik G, et al. Profile of cognitive complaints in vascular mild cognitive impairment and mild cognitive impairment. ISRN Neurol [Internet]. 2013;Article ID: 865827. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3830842&tool=pmcentrez&rendertype=abstract
*45. Duncan HD, Nikelski J, Pilon R, et al. Structural brain differences be-tween monolingual and multilingual patients with mild cognitive impairment and Alzheimer disease: Evidence for cognitive reserve. Neuropsychologia. 2018;109:270–82.
*46. Konsztowicz S, Anton J, Crane J, et al. A pilot study of training and compensation interventions for mild cognitive impairment. Dement Geriatr Cogn Dis Extra [Internet]. 2013;3(1):192–201. Available from: http://www.karger.com?doi=10.1159/000350026
47. Statistics Canada. Appendix 1: Structure of education and training in Canada. In: Education Indicators in Canada: Handbook for the Pan-Canadian Education Indicator Program. [Internet]. Ottawa, ON: Statistics Canada; 2012. Available from: https://www150.statcan.gc.ca/n1/pub/81-582-g/2012001/app-ann/app-ann1-eng.htm
48. Statistics Canada. Education Highlight Tables, 2016 Census. Highest level of educational attainment (general) by selected age groups 25 to 64, both sexes … [Internet]. Ottawa, ON: Statistics Canada, Census 2016; 2017. Available from: https://www12.statcan.gc.ca/census-recensement/2016/dp-pd/hlt-fst/edu-sco/Table.cfm?Lang=E&T=12&Geo=00&View=2&Age=2&SO=11A
49. Calgary Economic Development. Migration to Calgary [Internet]. Calgary, AB: The Department; 2019 [cited 2019 Oct 24]. Available from: https://www.calgaryeconomicdevelopment.com/research-and-reports/demographics-lp/migration/
50. Todd M, Davis KE, Cafferty TP. Who volunteers for adult development research? Research findings and practical steps to reach low volunteering groups. Int J Aging Hum Dev. 1984;18(3):177–84.
51. Petersen RC, Roberts RO, Knopman DS, et al. Prevalence of mild cognitive impairment is higher in men: The Mayo Clinic Study of Aging. Neurology. 2010;75(10):889–97.
52. Roberts RO, Geda YE, Knopman DS, et al. The incidence of MCI differs by subtype and is higher in men: The Mayo Clinic Study of Aging. Neurol-ogy. 2012;78(5):342–51.
53. Vassilaki M, Cha RH, Aakre JA, et al. Mortality in mild cognitive impair-ment varies by subtype, sex, and lifestyle factors: The Mayo Clinic Study of Aging. J Alzheimer’s Dis. 2015;45(4):1237–45.
54. Lin KA, Choudhury KR, Rathakrishnan BG, et al. Marked gender differ-ences in progression of mild cognitive impairment over 8 years. Alzheimer’s Dement Transl Res Clin Interv [Internet]. 2015;1(2):103–10. Available from: https://www.sciencedirect.com/science/article/pii/S2352873715000190
55. Au B, Dale-McGrath S, Tierney MC. Sex differences in the prevalence and incidence of mild cognitive impairment: a meta-analysis. Ageing Res Rev [Internet]. 2017;35:176–99. Available from: https://www.sciencedirect.com/science/article/pii/S1568163716301453
56. Fornazzari L, Fischer C, Hansen T, et al. Knowledge of Alzheimer’s disease and subjective memory impairment in Latin American seniors in the Greater Toronto Area. Int Psychogeriatrics. 2009;21(5):966–69.
57. Quan H, Fong A, De Coster C, et al. Variation in health services utilization among ethnic populations. Can Med Assoc J. 2006;174(6):787–91.
58. George S, Duran N, Norris K. A systematic review of barriers and facilitators to minority research participation among African Americans, Latinos, Asian Americans, and Pacific Islanders. Am J Public Health. 2014;104(2):e16–e31.
59. Calgary Economic Development. Fact Sheet : Calgary Small Business [Internet]. Calgary, AB: Calgary Economic Development; 2017. Available from: https://www.calgaryeconomicdevelopment.com/dmsdocument/166
60. Statistics Canada. Immigration and Ethnocultural Diversity in Canada. National Household Survey, 2011 [Internet]. Catalogue #99-010-X2011001. Ottawa, ON: Statistics Canada; 2013. Available from: http://www12.statcan.gc.ca/nhs-enm/2011/as-sa/99-010-x/99-010-x2011001-eng.pdf
61. Volkert J, Schulz H, Härter M, et al. The prevalence of mental disorders in older people in Western countries—a meta-analysis. Ageing Res Rev. 2013;12(1):339–53.
62. Kuerbis A, Sacco P, Blazer DG, et al. Substance abuse among older adults. Clin Geriatr Med. 2014;30(3):629–54.
63. Østybye T, Kristjansson B, Hill G, et al. Prevalence and predictors of depression in elderly Canadians: The Canadian Study of Health and Aging. Chron Dis Inj Can. 2005;26(4):93–99.
64. Rabins P V, Black B, German P, et al. The prevalence of psychiatric disorders in elderly residents of public housing. J Gerontol A Biol Sci Med Sci. 1996;51(6):M319–24.
65. Snowden MB, Atkins DC, Steinman LE, et al. Longitudinal association of dementia and depression. Am J Geriatr Psychiatry. 2015;23(9):897–905.
66. Cherbuin N, Kim S, Anstey KJ. Dementia risk estimates associated with measures of depression: a systematic review and meta-analysis. BMJ Open. 2015;5(12).
67. Langballe EM, Ask H, Holmen J, et al. Alcohol consumption and risk of dementia up to 27 years later in a large, population-based sample: the HUNT study, Norway. Eur J Epidemiol. 2015;30(9):1049–56.
68. Handing EP, Andel R, Kadlecova P, et al. Midlife alcohol consumption and risk of dementia over 43 years of follow-up: a population-based study from the Swedish Twin Registry. J Gerontol A Biol Sci Med Sci. 2015;70(10):1248–54.
69. Kaup AR, Byers AL, Falvey C, et al. Trajectories of depressive symptoms in older adults and risk of dementia. JAMA Psychiatry. 2016;73(5):525–31.
70. Ismail Z, Gatchel J, Bateman DR, et al. Affective and emotional dys-regulation as pre-dementia risk markers: exploring the mild behavioral impairment symptoms of depression, anxiety, irritability, and euphoria. Int Psychogeriatrics. 2018;30(02):185–96.
71. Rosenberg PB, Mielke MM, Appleby BS, et al. The association of neuropsychiatric symptoms in MCI with incident dementia and Alzheimer disease. Am J Geriatr Psychiatry. 2013;21(7):685–95.
72. Ismail Z, Malick A, Smith EE, et al. Depression versus dementia: is this construct still relevant? Neurodegener Dis Manag. 2014;4(2):119–26.
73. Almeida OP, Hankey GJ, Yeap BB, et al. Depression as a modifi-able factor to decrease the risk of dementia. Transl Psychiatry [Internet]. 2017;7(5):e1117. Available from: https://www.nature.com/articles/tp201790/
74. Tapiainen V, Hartikainen S, Taipale H, et al. Hospital-treated mental and behavioral disorders and risk of Alzheimer’s disease: a nationwide nested case-control study. Eur Psychiatry [Internet]. 2017;43:92–98. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0924933817327669
75. Singh-Manoux A, Dugravot A, Fournier A, et al. Trajectories of depressive symptoms before diagnosis of dementia: a 28-year follow up study. JAMA Psychiatry. 2017;74(7):712–18.
76. Ismail Z, Aguera-Ortiz L, Brodaty H, et al. The Mild Behavioral Impair-ment Checklist (MBI-C): a rating scale for neuropsychiatric symptoms in pre-dementia populations. J Alzheimer’s Dis. 2017;56(3):929–38.
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
325CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
77. Ismail Z, Smith EE, Geda Y, et al. Neuropsychiatric symptoms as early manifestations of emergent dementia: provisional diagnostic criteria for mild behavioral impairment. Alzheimer’s Dement. 2016;12(2):195–202.
78. Creese B, Brooker H, Ismail Z, et al. Mild behavioral impairment as a marker of cognitive decline in cognitively normal older adults. Am J Geriatr Psychiatry [Internet]. 2019;27(8):823–34. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1064748119302271
79. Mallo SC, Ismail Z, Pereiro AX, et al. Assessing Mild Behavioral Impair-ment with the Mild Behavioral Impairment-Checklist in people with mild cognitive impairment. J Alzheimers Dis. 2018;66(1):83–95.
80. Taragano FE, Allegri RF, Heisecke SL, et al. Risk of conversion to demen-tia in a mild behavioral impairment group compared to a psychiatric group and to a mild cognitive impairment group. J Alzheimer’s Dis. 2018;62(1):227–38.
81. Matsuoka T, Ismail Z, Narumoto J. Prevalence of mild behavioral impair-ment and risk of dementia in a psychiatric outpatient clinic. J Alzheimer’s Dis. 2019;70(2):505–13.
82. Ismail Z, Saykin AJ. Subjective cognitive decline (SCD) and mild be-havioral impairment (MBI): The intersection of two early indicators of AD pathophysiology. Alzheimer’s Dement J Alzheimer’s Assoc [Internet]. Poster presentation at the 2018 Alzheimer’s Association International Conference. 2018;14(7S Part 2-3):P1210. Available from: https://alz-journals.onlineli-brary.wiley.com/doi/abs/10.1016/j.jalz.2018.06.1697
83. Cano J, Chan V, Kan CN, et al. Mild behavioral impairment: prevalence in clinical setting and cognitive correlates. Alzheimer’s Dement [Internet]. Poster presentation at the 2018 Alzheimer’s Association International Confer-ence. 2018;14(7):P639–40. Available from: https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1016/j.jalz.2018.06.2685
84. Feder K, Michaud D, Ramage-Morin P, et al. Prevalence of hearing loss among Canadians aged 20 to 79: audiometric results from the 2012/2013 Canadian Health Measures Survey [Heal Reports]. Catalogue #82-003-X. Ottawa, ON: Statistics Canada; 2015.
85. National Coalition for Vision Health. Vision loss in Canada [Internet]. Ottawa, ON: Canadian Ophthalmological Society; 2011.
86. Millar WJ. Vision problems among seniors. Health Rep. 2004;16(1):45–49.
87. Aljied R, Aubin MJ, Buhrmann R, et al. Prevalence and determinants of visual impairment in Canada: cross-sectional data from the Canadian Longitudinal Study on Aging. Can J Ophthalmol [Internet]. 2018;53(3):291–97. Available from: https://www.sciencedirect.com/science/article/pii/S0008418217311353
88. Swenor BK, Ramulu PY, Willis JR, et al. The prevalence of concurrent hearing and vision impairment in the United States [research letter]. JAMA Intern Med. 2013;173(4):312–13.
89. Wei J, Hu Y, Zhang L, et al. Hearing impairment, mild cognitive impair-ment, and dementia: a meta-analysis of cohort studies. Dement Geriatr Cogn Disorders Extra. 2017;7(3):440–52.
90. Fischer ME, Cruickshanks KJ, Schubert CR, et al. Age-related sen-sory impairments and risk of cognitive impairment. J Am Geriatr Soc. 2016;64(10):1981–87.
91. Lin FR, Yaffe K, Xia J, et al. Hearing Loss and Cognitive Decline in Older Adults. JAMA Intern Med. 2013;173(4):293–99.
92. Ford AH, Hankey GJ, Yeap BB, et al. Hearing loss and the risk of dementia in later life. Maturitas. 2018;112:1–11.
93. Amieva H, Ouvrard C, Giulioli C, et al. Self-reported hearing loss, hearing aids, and cognitive decline in elderly adults: A 25-year study. J Am Geriatr Soc. 2015;63(10):2099–104.
94. Brenowitz WD, Kaup AR, Lin FR, et al. Multiple sensory impairment is associated with increased risk of dementia among black and white older adults. J Gerontol A Biol Sci Med Sci. 2019;74(6):890–96.
95. Loughrey DG, Kelly ME, Kelley GA, et al. Association of age-related hearing loss with cognitive function, cognitive impairment, and dementia. JAMA Otolaryngol Neck Surg. 2018;144(2):115–26.
96. LoBue C, Denney D, Hynan LS, et al. Self-reported traumatic brain injury
and mild cognitive impairment: increased risk and earlier age of diagnosis. J Alzheimer’s Dis. 2016;51(3):727–36.
97. Li W, Risacher SL, McAllister TW, et al. Traumatic brain injury and age at onset of cognitive impairment in older adults. J Neurology. 2017;263(7):1280–85.
98. LoBue C, Woon FL, Rossetti HC, et al. Traumatic brain injury history and progression from mild cognitive impairment to Alzheimer Disease. Neuropsychology. 2018;32(4):401–09.
99. Schaffert J, LoBue C, White CL, et al. Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer’s disease. Neuropsychology. 2018;32(4):410–16.
100. Fann JR, Ribe AR, Pedersen HS, et al. Long-term risk of dementia among people with traumatic brain injury in Denmark: a population-based observational cohort study. The Lancet Psychiatry. 2018;5(5):424–31.
101. Washington PM, Villapol S, Burns MP, et al. Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should it be classified together as traumatic encephalopathy? HHS Public Access. Exp Neurol [Internet]. 2016;275(3):381–88. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681695/pdf/nihms707585.pdf
102. Collins-Praino LE, Corrigan F. Does neuroinflammation drive the relationship between tau hyperphosphorylation and dementia develop-ment following traumatic brain injury? Brain Behav Immun [Internet]. 2017;60:369–82. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0889159116304366
103. Vassilaki M, Aakre JA, Cha RH, et al. Multimorbidity and risk of mild cognitive impairment. J Am Geriatr Soc. 2015 Sep;63(9):1783–90.
104. Koyanagi A, Lara E, Stubbs B, et al. Chronic physical conditions, multimorbidity, and mild cognitive impairment in low- and middle-income countries. J Am Geriatr Soc. 2018;66(4):721–27.
105. Ng TP, Feng L, Nyunt MSZ, et al. Metabolic syndrome and the risk of mild cognitive impairment and progression to dementia: follow-up of the Singapore longitudinal ageing study cohort. JAMA Neurol. 2016;73(4):456–63.
106. Pal K, Mukadam N, Petersen I, et al. Mild cognitive impairment and progression to dementia in people with diabetes, prediabetes and metabolic syndrome: a systematic review and meta-analysis. Soc Psychiatry Psychiatr Epidemiol [Internet]. 2018;53(11):1149–60. Available from: https://link.springer.com/article/10.1007/s00127-018-1581-3
107. Solfrizzi V, Scafato E, Capurso C, et al. Metabolic syndrome, mild cognitive impairment, and progression to dementia. The Italian Longitudinal Study on Aging. Neurobiol Aging. 2011;32(11):1932–41.
108. Sanmartin C. Research highlights on health and aging [Internet]. Catalogue #11-631-X. Ottawa, ON: Statistics Canada; 2016. Available from: https://www150.statcan.gc.ca/n1/pub/11-631-x/11-631-x2016001-eng.htm
109. Fu TS, Jing R, McFaull SR, et al. Recent trends in hospitalization and in-hospital mortality associated with traumatic brain injury in Canada: a nation-wide, population-based study. J Trauma Acute Care Surg. 2015;79(3):449–55.
110. Chan V, Zagorski B, Parsons D, et al. Older adults with acquired brain injury: a population based study. BMC Geriatr. 2013;13(1):97.
111. Rockwood K, Davis H, MacKnight C, et al. The consortium to investigate vascular impairment of cognition: methods and first findings. Can J Neurolog Sci. 2003;30(3):237–43. 112. The Canadian Study of Health Aging Working Group. Canadian Study of Health and Aging: study methods and prevalence of dementia. Can Med Assoc J. 1994;150(6):899–913.
113. Feldman H, Levy AR, Hsiung G-Y, et al. A Canadian cohort study of cognitive impairment and related dementias (ACCORD): study methods and baseline results. Neuroepidemiology. 2003;22(5):265–74.
114. Ebly EM, Hogan DB, Parhad IM. Cognitive impairment in the nonde-mented elderly—results from the Canadian Study of Health and Aging. Arch Neurol. 1995;52(612-619).
115. Gauthier S, Patterson C, Chertkow H, et al. Recommendations of the 4th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4). Can Geriatr J [Internet]. 2012;15(4):120–6. Available from: http://www.cgjonline.ca/index.php/cgj/article/view/49
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
326CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
†116. Petersen RC, Smith GE, Ivnik RJ, et al. Apolipoprotein E status as a predictor of the development of Alzheimer’s disease in memory-impaired individuals. J Am Med Assoc. 1995;273(16):1274–78.
*117. Massoud F, Chertkow H, Whitehead V, et al. Word-reading thresholds in Alzheimer disease and mild memory loss: a pilot study. Alzheimer Dis Assoc Disord. 2002;16(1):31–39.
†118. World Health Organization. International statistical classification of diseases and related health problems, 10th Revision. Geneva: WHO; 2016.
*119. Whatmough C, Chertkow H, Murtha S, et al. The semantic category effect increases with worsening anomia in Alzheimer’s type dementia. Brain Lang. 2003;84(1):134–47.
†120. Petersen RC, Smith GE, Tangalos EG, et al. Longitudinal outcome of patients with a mild cognitive impairment. Ann Neurol. 1993;34(2):294–95.
*121. Berlin D, Chong G, Chertkow H, et al. Evaluation of HFE (hemochro-matosis) mutations as genetic modifiers in sporadic AD and MCI. Neurobiol Aging. 2004;25(4):465–74.
†122. Petersen RC, Smith GE, Waring SC, et al. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56:303–09.
*123. Chantal S, Braun CMJ, Bouchard RW, et al. Similar 1H magnetic resonance spectroscopic metabolic pattern in the medial temporal lobes of patients with mild cognitive impairment and Alzheimer disease. Brain Res. 2004;1003(1-2):26–35.
†124. Petersen RC, Smith GE, Waring SC, et al. Aging, memory, and mild cognitive impairment. Int Psychogeriatrics. 1997;9(Suppl. 1):65–69.
*125. Geslani DM, Tierney MC, Herrmann N, et al. Mild cognitive impair-ment: an operational definition and its conversion rate to Alzheimer’s disease. Dement Geriatr Cogn Disord. 2005;19(5-6):383–89.
*126. Levinoff EJ, Saumier D, Chertkow H. Focused attention deficits in patients with Alzheimer’s disease and mild cognitive impairment. Brain Cogn. 2005;57(2):127–30.
*127. Belleville S, Gilbert B, Fontaine F, et al. Improvement of episodic memory in persons with mild cognitive impairment and healthy older adults: Evidence from a cognitive intervention program. Dement Geriatr Cogn Disord. 2006;22(5-6):486–99.
†128. Petersen RC, Doody R, Kurz A, et al. Current concepts in mild cogni-tive impairment. Arch Neurol. 2001;58(12):1985–92.
*129. Duong A, Whitehead V, Hanratty K, et al. The nature of lexico-semantic processing deficits in mild cognitive impairment. Neuropsychologia. 2006;44(10):1928–35.
†130. Chertkow H. Mild cognitive impairment. Curr Opin Neurol. 2002;15(4):401–07.
*131. Hudon C, Belleville S, Souchay C, et al. Memory for gist and detail information in Alzheimer’s disease and mild cognitive impairment. Neuro-psychology. 2006;20(5):566–77.
†132. Petersen RC. Mild cognitive impairment or questionable dementia? Arch Neurol. 2000;57(5):643–44.
*133. Murphy KJ, Rich JB, Troyer AK. Verbal fluency patterns in amnestic mild cognitive impairment are characteristic of Alzheimer’s type dementia. J Int Neuropsychol Soc. 2006;12(4):570–74.
*134. Belleville S, Chertkow H, Gauthier S. Working memory and control of attention in persons with Alzheimer’s disease and mild cognitive impairment. Neuropsychology. 2007;21(4):458–69.
†135. Petersen RC. Conceptual overview. In: Petersen RC, editor. Mild cognitive impairment: aging to Alzheimer’s disease. New York, NY: Oxford University Press; 2003. p. 1–14.
*136. Babins L, Slater ME, Whitehead V, et al. Can an 18-point clock-drawing scoring system predict dementia in elderly individuals with mild cognitive impairment? J Clin Exp Neuropsychol. 2008;30(2):173–86.
*137. Belleville S, Bherer L, Lepage É, et al. Task switching capacities in persons with Alzheimer’s disease and mild cognitive impairment. Neuropsy-chologia. 2008;46(8):2225–33.
*138. Clément F, Belleville S, Gauthier S. Cognitive complaint in mild cognitive impairment and Alzheimer’s disease. J Int Neuropsychol Soc. 2008;14(2):222–32.
*139. Djordjevic J, Jones-Gotman M, De Sousa K, et al. Olfaction in patients with mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging. 2008;29(5):693–706.
*140. Fellows L, Bergman H, Wolfson C, et al. Can clinical data predict pro-gression to dementia in amnestic mild cognitive impairment? Can J Neurol Sci. 2008;35(3):314–22.
*141. Murphy KJ, Troyer AK, Levine B, et al. Episodic, but not semantic, autobiographical memory is reduced in amnestic mild cognitive impairment. Neuropsychologia. 2008;46(13):3116–23.
*142. Troyer AK, Murphy KJ, Anderson ND, et al. Item and associative memory in amnestic mild cognitive impairment: performance on standard-ized memory tests. Neuropsychology. 2008;22(1):10–16.
*143. Troyer AK, Murphy KJ, Anderson ND, et al. Changing everyday memory behaviour in amnestic mild cognitive impairment: a randomised controlled trial. Neuropsychol Rehabil. 2008;18(1):65–88.
*144. Bélanger S, Belleville S. Semantic inhibition impairment in mild cognitive impairment: a distinctive feature of upcoming cognitive decline? Neuropsychology. 2009;23(5):592–606.
*145. Brambati SM, Belleville S, Kergoat MJ, et al. Single- and multiple-domain amnestic mild cognitive impairment: two sides of the same coin? Dement Geriatr Cogn Disord. 2009;28(6):541–49.
*146. Burton CL, Strauss E, Bunce D, et al. Functional abilities in older adults with mild cognitive Impairment. Gerontology. 2009;55(5):570–81.
†147. Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment–beyond controversies, towards a consensus: report of the International Work-ing Group on Mild Cognitive Impairment. J Intern Med. 2004;256(3):240–46.
*148. Clément F, Belleville S. Test-retest reliability of fMRI verbal episodic memory paradigms in healthy older adults and in persons with mild cognitive impairment. Hum Brain Mapp. 2009;30(12):4033–47.
*149. Clément F, Belleville S, Blanger S, et al. Personality and psycho-logical health in persons with mild cognitive impairment. Can J Aging. 2009;28(2):147–56.
*150. Hudon C, Belleville S, Gauthier S. The assessment of recognition memory using the Remember/Know procedure in amnestic mild cogni-tive impairment and probable Alzheimer’s disease. Brain Cogn [Internet]. 2009;70(1):171–79. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0278262609000220
*151. Montero-Odasso M, Casas A, Hansen KT, et al. Quantitative gait analysis under dual-task in older people with mild cognitive impairment: a reliability study. J Neuroeng Rehabil. 2009;6(1):35.
*152. Montero-Odasso M, Bergman H, Phillips NA, et al. Dual-tasking and gait in people with mild cognitive impairment. The effect of working memory. BMC Geriatr. 2009;9(1):1–8.
*153. Villeneuve S, Belleville S, Massoud F, et al. Impact of vascular risk factors and diseases on cognition in persons with mild cognitive impairment. Dement Geriatr Cogn Disord. 2009;27(4):375–81.
†154. Petersen RC, Morris JC. Mild cognitive impairment as a clinical entity and treatment target. Arch Neurol. 2005;62(7):1160–63.
*155. Arsenault-Lapierre G, Chertkow H, Lupien S. Seasonal effects on cor-tisol secretion in normal aging, mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging [Internet]. 2010;31(6):1051–54. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0197458008002558
*156. Bélanger S, Belleville S, Gauthier S. Inhibition impairments in Al-zheimer’s disease, mild cognitive impairment and healthy aging: effect of con-gruency proportion in a Stroop task. Neuropsychologia. 2010;48(2):581–90.
*157. Clément F, Belleville S. Compensation and disease severity on the memory-related activations in mild cognitive impairment. Biol Psychiatry [Internet]. 2010;68(10):894–902. Available from: http://www.scopus.com/inward/record.url?eid=2-s2.0-78049428087&partnerID=40&md5=bb77131d8cc34a93ab9d0919b23841a1
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
327CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
*158. Clément F, Belleville S, Mellah S. Functional neuroanatomy of the encoding and retrieval processes of verbal episodic memory in MCI. Cortex. 2010;46(8):1005–15.
*159. Jean L, Simard M, Wiederkehr S, et al. Efficacy of a cognitive training programme for mild cognitive impairment: results of a randomised controlled study. Neuropsychol Rehabil. 2010;20(3):377–405.
*160. Joubert S, Brambati SM, Ansado J, et al. The cognitive and neural ex-pression of semantic memory impairment in mild cognitive impairment and early Alzheimer’s disease. Neuropsychologia [Internet]. 2010;48(4):978–88. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0028393209004515
*161. McLaughlin PM, Borrie MJ, Murtha SJE. Shifting efficacy, distribu-tion of attention and controlled processing in two subtypes of mild cognitive impairment: response time performance and intraindividual variability on a visual search task. Neurocase. 2010;16(5):408–17.
*162. Montero-Odasso M, Muir SW. Simplifying detection of mild cognitive impairment subtypes. J Am Geriatr Soc. 2010;58(5):992–94.
*163. Sylvain-Roy S, Bherer L, Belleville S. Contribution of temporal prepar-ation and processing speed to simple reaction time in persons with Alzheim-er’s disease and mild cognitive impairment. Brain Cogn. 2010;74(3):255–61.
*164. Arsenault-Lapierre G, Whitehead V, Belleville S, et al. Mild cogni-tive impairment subcategories depend on the source of norms. J Clin Exp Neuropsychol. 2011;33(5):596–603.
*165. Belleville S, Clément F, Mellah S, et al. Training-related brain plasticity in subjects at risk of developing Alzheimer’s disease. Brain. 2011;134(6):1623–34.
*166. Belleville S, Ménard MC, Lepage É. Impact of novelty and type of material on recognition in healthy older adults and persons with mild cognitive impairment. Neuropsychologia [Internet]. 2011;49(10):2856–65. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0028393211002922
*167. Brunet J, Hudon C, Macoir J, et al. The relation between depressive symptoms and semantic memory in amnestic mild cognitive impairment and in late-life depression. J Int Neuropsychol Soc. 2011;17:865–74.
*168. Gagnon LG, Belleville S. Working memory in mild cognitive impair-ment and Alzheimer’s disease: contribution of forgetting and predictive value of complex span tasks. Neuropsychology. 2011;25(2):226–36.
†169. Gauthier S, Reisberg B, Zaudig M, et al. Mild cognitive impairment. Lancet [Internet]. 2006;367(9518):1262–70. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0140673606685425
*170. Gao FQ, Swartz RH, Scheltens P, et al. Complexity of MRI white matter hyperintensity assessments in relation to cognition in aging and dementia from the Sunnybrook Dementia Study. J Alzheimer’s Dis. 2011;26(s3):379–88.
*171. Hudon C, Villeneuve S, Belleville S. The effect of semantic orien-tation at encoding on free-recall performance in amnestic mild cognitive impairment and probable Alzheimer’s disease. J Clin Exp Neuropsychol. 2011;33(6):631–38.
*172. Matteau E, Dupré N, Langlois M, et al. Mattis Dementia Rating Scale 2: screening for MCI and dementia. Am J Alzheimers Dis Other Demen. 2011;26(5):389–98.
*173. Muir SW, Speechley M, Wells J, et al. Gait assessment in mild cogni-tive impairment and Alzheimer’s disease: the effect of dual-task challenges across the cognitive spectrum. Gait Posture [Internet]. 2012;35(1):96–100. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0966636211002578
*174. Protzner AB, Mandzia JL, Black SE, et al. Network interactions explain effective encoding in the context of medial temporal damage in MCI. Hum Brain Mapp. 2011;32(8):1277–89.
*175. Rupsingh R, Borrie M, Smith M, et al. Reduced hippocampal gluta-mate in Alzheimer disease. Neurobiol Aging [Internet]. 2011;32(5):802–10. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0197458009001626
*176. Sherwin BB, Chertkow H, Schipper H, et al. A randomized controlled trial of estrogen treatment in men with mild cognitive impairment. Neurobiol Aging [Internet]. 2011;32(10):1808–17. Available from: https://www.scien-cedirect.com/science/article/abs/pii/S0197458009003613
*177. Vandermorris S, Hultsch DF, Hunter MA, et al. Including persistency of impairment in mild cognitive impairment classification enhances prediction of 5-year decline. Arch Clin Neuropsychol. 2011;26(1):26–37.
*178. Villeneuve S, Massoud F, Bocti C, et al. The nature of episodic memory deficits in MCI with and without vascular burden. Neuropsychologia [Inter-net]. 2011;49(11):3027–35. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0028393211003253
*179. Arsenault-Lapierre G, Bergman H, Chertkow H. Word reading threshold and mild cognitive impairment: a validation study. BMC Geriatr [Internet]. 2012;12(1):38. Available from: http://bmcgeriatr.biomedcentral.com/arti-cles/10.1186/1471-2318-12-38
*180. Arsenault-Lapierre G, Whitehead V, Lupien S, et al. Effects of anosog-nosia on perceived stress and cortisol levels in Alzheimer’s disease. Int J Alzheimers Dis. 2012;2012:Article ID: 209570.
*181. Clément F, Belleville S. Effect of disease severity on neural compen-sation of item and associative recognition in mild cognitive impairment. J Alzheimer’s Dis. 2012;29(1):109–23.
*182. Gagnon LG, Belleville S. Training of attentional control in mild cognitive impairment with executive deficits: results from a double-blind randomised controlled study. Neuropsychol Rehabil. 2012;22(6):809–35.
*183. Morin J-F, Mouiha A, Pietrantonio S, et al. Structural neuroimaging of concomitant depressive symptoms in amnestic mild cognitive impairment: a pilot study. Dement Geriatr Cogn Dis Extra [Internet]. 2012;2(1):573–88. Available from: https://www.karger.com/Article/FullText/345234%0Ahttp://www.ncbi.nlm.nih.gov/pubmed/23277788%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3522455
*184. Rainville C, Lepage E, Gauthier S, et al. Executive function deficits in persons with mild cognitive impairment: a study with a Tower of London task. J Clin Exp Neuropsychol. 2012;34(3):306–24.
*185. Troyer AK, Murphy KJ, Anderson ND, et al. Associative recogni-tion in mild cognitive impairment: relationship to hippocampal volume and apolipoprotein E. Neuropsychologia [Internet]. 2012;50(14):3721–28. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0028393212004563
†186. Knopman DS, Boeve BF, Petersen RC. Essentials of the proper diagnoses of mild cognitive impairment, dementia, and major subtypes of dementia. Mayo Clin Proc. 2003;78(10):1290–308.
*187. Villeneuve S, Belleville S. The nature of memory failure in mild cognitive impairment: examining association with neurobiological markers and effect of progression. Neurobiol Aging [Internet]. 2012;33(9):1967–78. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0197458011003988
*188. Ansado J, Collins L, Joubert S, et al. Interhemispheric coupling improves the brain’s ability to perform low cognitive demand tasks in Alzheimer’s disease and high cognitive demand tasks in normal aging. Neuropsychology. 2013;27(4):464–80.
*189. Clément F, Gauthier S, Belleville S. Executive functions in mild cog-nitive impairment: Emergence and breakdown of neural plasticity. Cortex. 2013;49(5):1268–79.
*190. Guild EB, Vasquez BP, Maione AM, et al. Dynamic working memory performance in individuals with single-domain amnestic mild cognitive im-pairment. J Clin Exp Neuropsychol [Internet]. 2014;36(7):751–60. Available from: https://www.tandfonline.com/doi/abs/10.1080/13803395.2014.941790
*191. Julayanont P, Brousseau M, Chertkow H, et al. Montreal Cognitive Assessment Memory Index Score (MoCA-MIS) as a predictor of conversion from mild cognitive impairment to Alzheimer’s disease. J Am Geriatr Soc. 2014;62(4):679–84.
*192. McLaughlin PM, Anderson ND, Rich JB, et al. Visual selective atten-tion in amnestic mild cognitive impairment. J Gerontol B Psychol Sci Soc Sci. 2014;69(6):881–91.
HUANG: MCI PARTICIPANTS IN CANADIAN RESEARCH PROTOCOLS
328CANADIAN GERIATRICS JOURNAL, VOLUME 23, ISSUE 4, DECEMBER 2020
*193. Peltsch A, Hemraj A, Garcia A, et al. Saccade deficits in amnestic mild cognitive impairment resemble mild Alzheimer’s disease. Eur J Neurosci. 2014;39(11):2000–13.
*194. Peters F, Villeneuve S, Belleville S. Predicting progression to dementia in elderly subjects with mild cognitive impairment using both cognitive and neuroimaging predictors. J Alzheimer’s Dis. 2014;38(2):307–18.
*195. Wu L, Soder RB, Schoemaker D, et al. Resting state executive control network adaptations in amnestic mild cognitive impairment. J Alzheimer’s Dis. 2014;40(4):993–1004.
*196. Callahan BL, Joubert S, Tremblay M-P, et al. Semantic memory impair-ment for biological and man-made objects in individuals with amnestic mild cognitive impairment or late-life depression. J Geriatr Psychiatry Neurol. 2015;28(2):108–16.
*197. Cloutier S, Chertkow H, Kergoat MJ, et al. Patterns of cognitive decline prior to dementia in persons with mild cognitive impairment. J Alzheimer’s Dis. 2015;47(4):901–13.
*198. Gaudreau G, Monetta L, Macoir J, et al. Mental state inferences abil-ities contribution to verbal irony comprehension in older adults with mild cognitive impairment. Behav Neurol. 2015;2015. Article ID 685613.
*199. Le Page A, Bourgade K, Lamoureux J, et al. NK cells are activated in amnestic mild cognitive impairment but not in mild Alzheimer’s disease patients. J Alzheimer’s Dis. 2015;46(1):93–107.
†200. Grundman M, Petersen RC, Ferris SH, et al. Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. Arch Neurol [Internet]. 2004;61(1):59–66. Available from: https://jamanetwork.com/journals/jamaneurology/article-abstract/785241
*201. Ten Brinke LF, Bolandzadeh N, Nagamatsu LS, et al. Aerobic exercise increases hippocampal volume in older women with probable mild cogni-tive impairment: a 6-month randomised controlled trial. Br J Sports Med. 2015;49(4):248–54.
*202. Brayet P, Petit D, Frauscher B, et al. Quantitative EEG of rapid-eye-movement sleep: a marker of amnestic mild cognitive impairment. Clin EEG Neurosci. 2016;47(2):134–41.
*203. Burhan AM, Anazodo UC, Chung JK, et al. The effect of task-irrelevant fearful-face distractor on working memory processing in mild cognitive impairment versus healthy controls: an exploratory fMRI study in female participants. Behav Neurol. 2016;2016. Article #1637392.
*204. Callahan BL, Simard M, Mouiha A, et al. Impact of depressive symp-toms on memory for emotional words in mild cognitive impairment and late-life depression. J Alzheimer’s Dis. 2016;52(2):451–62.
*205. Langlois R, Joubert S, Benoit S, et al. Memory for public events in mild cognitive impairment and Alzheimer’s disease: the importance of rehearsal. J Alzheimer’s Dis. 2016;50(4):1023–33.
*206. Nasreddine ZS, Patel BB. Validation of Montreal Cognitive Assessment, MoCA, aAlternate French versions. Can J Neurol Sci. 2016;43(5):665–71.
*207. Vallet GT, Rouleau I, Benoit S, et al. Alzheimer’s disease and memory strength: gradual decline of memory traces as a function of their strength. J Clin Exp Neuropsychol [Internet]. 2016;38(6):648–60. Available from: https://www.tandfonline.com/doi/abs/10.1080/13803395.2016.1147530
*208. Bocti C, Pépin F, Tétreault M, et al. Orthostatic hypotension associ-ated with executive dysfunction in mild cognitive impairment. J Neurol Sci [Internet]. 2017;382:79–83. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0022510X17343186
*209. Callahan BL, Laforce R, Dugas M, et al. Memory for emotional images differs according to the presence of depressive symptoms in individuals at risk for dementia. Int Psychogeriatrics. 2017;29(4):673–85.
*210. Crockett RA, Hsu CL, Best JR, et al. Resting state default mode net-work connectivity, dual task performance, gait speed, and postural sway in older adults with mild cognitive impairment. Front Aging Neurosci [Internet]. 2017;9(December):1–9. Available from: http://journal.frontiersin.org/arti-cle/10.3389/fnagi.2017.00423/full
*211. Knezevic D, Verhoeff NPL, Hafizi S, et al. Imaging microglial activa-tion and amyloid burden in amnestic mild cognitive impairment. J Cereb Blood Flow Metab. 2018;38(11):1885–95.
*212. Le Page A, Lamoureux J, Bourgade K, et al. Polymorphonuclear neutro-phil functions are differentially altered in amnestic mild cognitive impairment and mild Alzheimer’s disease patients. J Alzheimer’s Dis. 2017;60(1):23–42.
*213. Mah L, Anderson ND, Verhoeff NPLG, et al. Negative emotional verbal memory biases in mild cognitive impairment and late-onset de-pression. Am J Geriatr Psychiatry [Internet]. 2017;25(10):1160–70. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1064748117303135?via%3Dihub
*214. Montero-Odasso MM, Sarquis-Adamson Y, Speechley M, et al. Asso-ciation of dual-task gait with incident dementia in mild cognitive impairment: results from the Gait and Brain Study. JAMA Neurol. 2017;74(7):857–65.
*215. O’Caoimh R, Gao Y, Svendovski A, et al. Comparing approaches to optimize cut-off scores for short cognitive screening instruments in mild cognitive impairment and dementia. J Alzheimer’s Dis. 2017;57(1):123–33.
*216. Belleville S, Hudon C, Bier N, et al. MEMO+: Efficacy, durability and effect of cognitive training and psychosocial intervention in individuals with mild cognitive impairment. J Am Geriatr Soc. 2018;66(4):655–63.
*217. Croteau E, Castellano CA, Fortier M, et al. A cross-sectional com-parison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer’s disease. Exp Geron-tol [Internet]. 2018;107:18–26. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0531556517302280
*218. Goodman MS, Kumar S, Zomorrodi R, et al. Theta-gamma coupling and working memory in Alzheimer’s dementia and mild cognitive impair-ment. Front Aging Neurosci. 2018;10(Apr):101.
†219. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5®), 5th ed. Washington, DC: American Psychiatric Publication; 2013.
*220. Hsu CL, Best JR, Voss MW, et al. Functional neural correlates of slower gait among older adults with mild cognitive impairment. J Gerontol A Biol Sci Med Sci [Internet]. 2018;74(4):513–18. Available from: https://academic.oup.com/biomedgerontology/article/74/4/513/4868628
*221. Villeneuve S, Rodrigues-Brazète J, Joncas S, et al. Validity of the Mattis Dementia Rating Scale to detect mild cognitive impairment in Parkinson’s disease and REM sleep behavior disorder. Dement Geriatr Cogn Disord. 2011;31(3):210–17.
†222. Litvan I, Goldman JG, Tröster AI, et al. Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: Movement Disorder Society Task Force guidelines. Mov Disord. 2012;27(3):349–56.
*223. Christopher L, Marras C, Duff-Canning S, et al. Combined insular and striatal dopamine dysfunction are associated with executive deficits in Parkin-son’s disease with mild cognitive impairment. Brain. 2014;137(2):565–75.
*224. Hanganu A, Bedetti C, Degroot C, et al. Mild cognitive impairment is linked with faster rate of cortical thinning in patients with Parkinson’s disease longitudinally. Brain. 2014;137(4):1120–29.
Correspondence to: Brandy L. Callahan, PhD, Department of Psychology, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada T2N 1N4 E-mail: [email protected]